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沢津橋俊

徳島大学

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2024年4月19日更新

職名: 准教授
電話: 088-633-7426
電子メール: shun-sawa2@tokushima-u.ac.jp
学歴: 2000/3: 静岡大学理学部生物地球環境科学科卒業
2002/3: 静岡大学大学院理工学研究科生物地球環境科学専攻博士前期課程修了修士(理学)
2005/9: 東京大学大学院農学生命科学研究科応用生命工学専攻博士課程修了博士(農学)
学位: 博士(農学) (東京大学) (2005年9月)
職歴・経歴: 2005/10: 東京大学分子細胞生物学研究所博士研究員
2006/4: 科学技術振興機構戦略的創造研究推進事業 (JST・ERATO) プロジェクト研究員
2010/3: 群馬大学生体調節研究所助教
2014/3: 徳島大学藤井節郎記念医科学センター特任助教
2014/12: 徳島大学藤井節郎記念医科学センター特任講師
2016/4: 徳島大学先端酵素学研究所オープンイノベーション領域特任講師

専門分野・研究分野: 分子生物学 (Molecular Biology)

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2024年4月19日更新

専門分野・研究分野: 分子生物学 (Molecular Biology)
担当経験のある授業科目: 研究者総覧に該当データはありませんでした。
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2024年4月19日更新

専門分野・研究分野: 分子生物学 (Molecular Biology)

研究テーマ: 脂溶性ビタミン・ステロイドホルモンによる核内受容体転写機構の研究

著書

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論文

Bingzi Dong, Masahiro Hiasa, Yoshiki Higa, Yukiyo Ohnishi, Itsuro Endo, Takeshi Kondo, Yuichi Takashi, Maria Tsoumpra, Risa Kainuma, Shun Sawatsubashi, Hiroshi Kiyonari, Go Shioi, Hiroshi Sakaue, Tomoki Nakashima, Shigeaki Kato, Masahiro Abe, Seiji Fukumoto and Toshio Matsumoto :
Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis.,
Nature Communications, Vol.13, No.1, 2022.

(要約): did not exhibit any abnormalities. We demonstrate that osteoblast/osteocyte-derived IL-11 controls both osteogenesis and systemic adiposity in response to mechanical loading, an important insight for our understanding of osteoporosis and metabolic syndromes.
(キーワード): Animals / Mice / Adipogenesis / Interleukin-11 / Obesity / Osteoblasts / Osteocytes / Osteogenesis / Mice, Knockout
(徳島大学機関リポジトリ): ● Metadata: 118940
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41467-022-34869-3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36424386; ● Search Scopus @ Elsevier (PMID): 36424386; ● Search Scopus @ Elsevier (DOI): 10.1038/s41467-022-34869-3

(徳島大学機関リポジトリ: 118940, DOI: 10.1038/s41467-022-34869-3, PubMed: 36424386) Takumi Kouketsu, Rina Monma, Yuri Miyairi, Shun Sawatsubashi, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara and Atsushi Yokoyama :
IRF2BP2 is a novel HNF4α co-repressor: Its role in gluconeogenic gene regulation via biochemically labile interaction.,
Biochemical and Biophysical Research Communications, Vol.615, 81-87, 2022.

(要約): Hepatocyte nuclear factor 4α (HNF4α) has essential roles in controlling the expression of a variety of genes involved in key metabolic pathways, including gluconeogenesis in the liver. The mechanistic and physiological significance of peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) for HNF4α-mediated transcriptional activation models for gluconeogenic genes is well characterized. However, the transcriptional repression of HNF4α for those genes remains to be examined. In this study, we applied novel proteomic techniques to evaluate the interactions of HNF4α, including those with biochemically labile binding proteins. Based upon our experiments, we identified interferon regulatory factor 2 binding protein 2 (IRF2BP2) as a novel HNF4α co-repressor. This interaction could not be detected by conventional immunoprecipitation. IRF2BP2 repressed the transcriptional activity of HNF4α dependent on its E3 ubiquitin ligase activity. Deficiency of the IRF2BP2 gene in HepG2 cells induced gluconeogenic genes comparable to that of forskolin-treated wild-type HepG2 cells. Together, these results suggest that IRF2BP2 represents a novel class of nuclear receptor co-regulator.
(キーワード): Co-Repressor Proteins / Gene Expression Regulation / Gluconeogenesis / Hepatocyte Nuclear Factor 4 / Liver / Proteomics
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2022.04.133
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35609419; ● Search Scopus @ Elsevier (PMID): 35609419; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2022.04.133

(DOI: 10.1016/j.bbrc.2022.04.133, PubMed: 35609419) Atsushi Yokoyama, Takumi Kouketsu, Yuri Otsubo, Erika Noro, Shun Sawatsubashi, Hiroki Shima, Ikuro Satoh, Sadafumi Kawamura, Takashi Suzuki, Kazuhiko Igarashi and Akira Sugawara :
Identification and Functional Characterization of a Novel Androgen Receptor Coregulator, EAP1.,
Journal of the Endocrine Society, Vol.5, No.11, 2021.

(要約): The androgen receptor (AR) plays an essential role in the development of prostate cancer, and androgen-deprivation therapy is used as a first-line treatment for prostate cancer. However, under androgen-deprivation therapy, castration-resistant prostate cancer inevitably arises, suggesting that the interacting transcriptional coregulators of AR are promising targets for developing novel therapeutics. In this study, we used novel proteomic techniques to evaluate the AR interactome, including biochemically labile binding proteins, which might go undetected by conventional purification methods. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, we identified enhanced at puberty 1 (EAP1) as a novel AR coregulator, whereas its interaction with AR could not be detected under standard biochemical conditions. EAP1 enhanced the transcriptional activity of AR via the E3 ubiquitin ligase activity, and its ubiquitination substrate proteins included AR and HDAC1. Furthermore, in prostate cancer specimens, EAP1 expression was significantly correlated with AR expression as well as a poor prognosis of prostate cancer. Together, these results suggest that EAP1 is a novel AR coregulator that promotes AR activity and potentially plays a role in prostate cancer progression.
(出版サイトへのリンク): ● Publication site (DOI): 10.1210/jendso/bvab150
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34585037; ● Search Scopus @ Elsevier (PMID): 34585037; ● Search Scopus @ Elsevier (DOI): 10.1210/jendso/bvab150

(DOI: 10.1210/jendso/bvab150, PubMed: 34585037) Yuichi Takashi, Shun Sawatsubashi, Itsuro Endo, Yukiyo Ohnishi, Masahiro Abe, Munehide Matsuhisa, Daiji Kawanami, Toshio Matsumoto and Seiji Fukumoto :
Skeletal FGFR1 signaling is necessary for regulation of serum phosphate level by FGF23 and normal life span.,
Biochemistry and Biophysics Reports, Vol.27, 101107, 2021.

(要約): Fibroblast growth factor (FGF) 23 produced by the bone is the principal hormone to regulate serum phosphate level. Serum FGF23 needs to be tightly regulated to maintain serum phosphate in a narrow range. Thus, we hypothesized that the bone has some phosphate-sensing mechanism to regulate the production of FGF23. Previously we showed that extracellular phosphate induces the phosphorylation of FGF receptor 1 (FGFR1) and FGFR1 signaling regulates the expression of , whose product works to increase FGF23 production . In this study, we show the significance of FGFR1 in the regulated FGF23 production and serum phosphate level . We generated late-osteoblast/osteocyte-specific -knockout mice ( ) by crossing the and the floxed mouse lines. We evaluated serum phosphate and FGF23 levels, the expression of in the bone, the body weight and life span. A selective ablation of aborted the increase of serum active full-length FGF23 and the enhanced expression of in the bone by a high phosphate diet. These mice showed more pronounced hyperphosphatemia compared with control mice. In addition, these mice fed with a control diet showed body weight loss after 23 weeks of age and shorter life span. These results reveal a novel significance of FGFR1 signaling in the phosphate metabolism and normal life span.
(徳島大学機関リポジトリ): ● Metadata: 116283
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrep.2021.101107
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34458594; ● Search Scopus @ Elsevier (PMID): 34458594; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrep.2021.101107

(徳島大学機関リポジトリ: 116283, DOI: 10.1016/j.bbrep.2021.101107, PubMed: 34458594) Yoshiaki Kanemoto, Akira Hayakawa, Takahiro Sawada, Rei Amano, Tomohiro Kurokawa, Shun Sawatsubashi, Seiji Fukumoto, Jinichi Mori and Shigeaki Kato :
Transcriptional Regulation of 25-Hydroxyvitamin D-24-Hydroxylase (CYP24A1) by Calcemic Factors in Keratinocytes.,
Journal of Nutritional Science and Vitaminology, Vol.67, No.6, 424-428, 2021.

(要約): CYP24A1 regulates serum vitamin D (VD) levels by inactivating 25(OH)D, which is the precursor of the active form of VD [1 ,25(OH)D], and CYP24A1 expression is controlled by multiple calcemic factors such as 1 ,25(OH)D, calcium, and phosphate. A major phosphaturic factor, FGF23, has also been identified as a regulator of serum VD levels by affecting renal CYP24A1 gene expression; however, its effect on CYP24A1 in extrarenal cells remains largely unstudied. Therefore, the direct effect of FGF23 on CYP24A1 was examined in a human keratinocyte cell line (HaCaT). In this cell line, significant induction of CYP24A1 gene expression by 1 ,25(OH)D was seen within 4 h by qRT-PCR, and this was mediated by the VD receptor, as shown in a mutant cell line genetically deficient in this receptor. However, FGF23 treatment up to 12 h did not induce CYP24A1 expression, although the expected activation of the downstream MAPK signaling pathway was seen. High calcium and phosphate treatments were also ineffective in inducing CYP24A1 gene expression. Furthermore, a luciferase assay showed no activation of a VD-sensitive proximal CYP24A1 promoter in response to the calcium and phosphate treatments, suggesting that the effect of FGF23 on dermal CYP24A1 gene expression is indirect. From these findings, we speculate that CYP24A1 gene regulation by FGF23 occurs mainly in renal cells, but not in extrarenal cells, at least not in keratinocytes.
(キーワード): Calcitriol / Humans / Keratinocytes / Receptors, Calcitriol / ビタミンD (vitamin D) / Vitamin D3 24-Hydroxylase
(出版サイトへのリンク): ● Publication site (DOI): 10.3177/jnsv.67.424
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34980721; ● Search Scopus @ Elsevier (PMID): 34980721; ● Search Scopus @ Elsevier (DOI): 10.3177/jnsv.67.424

(DOI: 10.3177/jnsv.67.424, PubMed: 34980721) Maria Tsoumpra, Shun Sawatsubashi, Michihiro Imamura, Seiji Fukumoto, Shin'ichi Takeda, Toshio Matsumoto and Yoshitsugu Aoki :
Dystrobrevin alpha gene is a direct target of the vitamin D receptor in muscle.,
Journal of Molecular Endocrinology, Vol.64, No.3, 195-208, 2020.

(要約): The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (VD3), exerts its tissue-specific actions through binding to its intracellular vitamin D receptor (VDR) which functions as a heterodimer with retinoid X receptor (RXR) to recognize vitamin D response elements (VDRE) and activate target genes. Upregulation of VDR in murine skeletal muscle cells occurs concomitantly with transcriptional regulation of key myogenic factors upon VD3 administration, reinforcing the notion that VD3 exerts beneficial effects on muscle. Herein we elucidated the regulatory role of VD3/VDR axis on the expression of dystrobrevin alpha (DTNA), a member of dystrophin-associated protein complex (DAPC). In C2C12 cells, Dtna and VDR gene and protein expression were upregulated by 1-50 nM of VD3 during all stages of myogenic differentiation. In the dystrophic-derived H2K-mdx52 cells, upregulation of DTNA by VD3 occurred upon co-transfection of VDR and RXR expression vectors. Silencing of MyoD1, an E-box binding myogenic transcription factor, did not alter the VD3-mediated Dtna induction, but Vdr silencing abolished this effect. We also demonstrated that VD3 administration enhanced the muscle-specific Dtna promoter activity in presence of VDR/RXR only. Through site-directed mutagenesis and chromatin immunoprecipitation assays, we have validated a VDRE site in Dtna promoter in myogenic cells. We have thus proved that the positive regulation of Dtna by VD3 observed during in vitro murine myogenic differentiation is VDR mediated and specific. The current study reveals a novel mechanism of VDR-mediated regulation for Dtna, which may be positively explored in treatments aiming to stabilize the DAPC in musculoskeletal diseases.
(出版サイトへのリンク): ● Publication site (DOI): 10.1530/JME-19-0229
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31940280; ● Search Scopus @ Elsevier (PMID): 31940280; ● Search Scopus @ Elsevier (DOI): 10.1530/JME-19-0229

(DOI: 10.1530/JME-19-0229, PubMed: 31940280) Seiji Fukumoto, Yuichi Takashi, Maria Tsoumpra, Shun Sawatsubashi and Toshio Matsumoto :
How do we sense phosphate to regulate serum phosphate level?,
Journal of Bone and Mineral Metabolism, Vol.38, No.1, 1-6, 2020.

(要約): Abnormal phosphate levels result in several pathological conditions such as rickets/osteomalacia and ectopic calcification indicating that there must be a system that regulates phosphate level within a narrow range. FGF23 has been shown to be an essential hormone regulating serum phosphate level. FGF23 binds to Klotho-FGF receptor complex to reduce serum phosphate level. Several reports suggested that FGF receptor is involved in the regulation of FGF23 production. It has been also shown that high extracellular phosphate can activate several intracellular signaling pathways. However, it has been unclear whether and how phosphate regulates FGF23 production in vivo. Our recent results indicate that high extracellular phosphate directly activates FGF receptor 1 and the downstream intracellular signaling enhances FGF23 production. Thus, there is a negative feedback system for the regulation of serum phosphate level involving FGF receptor and FGF23. We propose that FGF receptor works at least as one of phosphate sensors in the maintenance of serum phosphate level.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00774-019-01066-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31797064; ● Search Scopus @ Elsevier (PMID): 31797064; ● Search Scopus @ Elsevier (DOI): 10.1007/s00774-019-01066-0

(DOI: 10.1007/s00774-019-01066-0, PubMed: 31797064) Yuichi Takashi, Hidetaka Kosako, Shun Sawatsubashi, Yuka Kinoshita, Nobuaki Ito, Maria K. Tsoumpra, Masaomi Nangaku, Masahiro Abe, Munehide Matsuhisa, Shigeaki Kato, Toshio Matsumoto and Seiji Fukumoto :
Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation,
Proceedings of the National Academy of Sciences of the United States of America, Vol.116, No.23, 11418-11427, 2019.

(要約): Fibroblast growth factor (FGF) 23 produced by bone is a hormone that decreases serum phosphate (Pi). Reflecting its central role in Pi control, serum FGF23 is tightly regulated by serum Pi alterations. FGF23 levels are regulated by the transcriptional event and posttranslational cleavage into inactive fragments before its secretion. For the latter, O-glycosylation of FGF23 by gene product prevents the cleavage, leading to an increase in serum FGF23. However, the molecular basis of Pi sensing in the regulation of serum FGF23 remains elusive. In this study, we showed that high Pi diet enhanced the skeletal expression of , but not , with expected increases in serum FGF23 and Pi in mice. induction by high Pi was further observed in osteoblastic UMR 106 cells, and this was mediated by activation of the extracellular signal-regulated kinase (ERK) pathway. Through proteomic searches for the upstream sensor for high Pi, we identified one subtype of the FGF receptor (FGFR1c), which was phosphorylated by high Pi in the absence of FGFs. The mode of unliganded FGFR activation by high Pi appeared different from that of FGFR bound to a canonical FGFR ligand (FGF2) when phosphorylation of the FGFR substrate 2α and ERK was monitored. Finally, we showed that an FGFR inhibitor and conditional deletion of in osteoblasts/osteocytes abrogated high Pi diet-induced increases in serum FGF23 and femoral expression in mice. Thus, these findings uncover an unrecognized facet of unliganded FGFR function and illustrate a Pi-sensing pathway involved in regulation of FGF23 production.
(徳島大学機関リポジトリ): ● Metadata: 113621
(出版サイトへのリンク): ● Publication site (DOI): 10.1073/pnas.1815166116
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31097591; ● Search Scopus @ Elsevier (PMID): 31097591; ● Search Scopus @ Elsevier (DOI): 10.1073/pnas.1815166116

(徳島大学機関リポジトリ: 113621, DOI: 10.1073/pnas.1815166116, PubMed: 31097591) Shun Sawatsubashi, Koichi Nishimura, Jinichi Mori, Alexander Kouzmenko and Shigeaki Kato :
The Function of the Vitamin D Receptor and a Possible Role of Enhancer RNA in Epigenomic Regulation of Target Genes: Implications for Bone Metabolism.,
Journal of Bone Metabolism, Vol.26, No.1, 3-12, 2019.

(要約): Vitamin D (VD) is essential for bone health, and VD or its analogues are widely used in clinics to ameliorate bone loss. The targets and mode of VD anti-osteoporotic actions appear to be different from those of other classes of drugs modulating bone remodeling. VD exerts its biological activities through the nuclear VD receptor (VDR)-mediated transcriptional regulation of target mRNA and non-coding RNA genes. VD-induced gene regulation involves epigenetic modifications of chromatin conformation at the target loci as well as reconfiguration of higher-order chromosomal organization through VDR-mediated recruitment of various regulatory factors. Enhancer RNAs (eRNA), a class of non-coding enhancer-derived RNAs, have recently emerged as VDR target gene candidates that act through reorganization of chromatin looping to induce enhancer-promoter interaction in activation of mRNA-encoding genes. This review outlines the molecular mechanisms of VD actions mediated by the VDR and suggests novel function of eRNAs in VDR transactivation.
(出版サイトへのリンク): ● Publication site (DOI): 10.11005/jbm.2019.26.1.3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30899718; ● Search Scopus @ Elsevier (PMID): 30899718; ● Search Scopus @ Elsevier (DOI): 10.11005/jbm.2019.26.1.3

(DOI: 10.11005/jbm.2019.26.1.3, PubMed: 30899718) Shun Sawatsubashi, Yudai Joko, Seiji Fukumoto, Toshio Matsumoto and Shigeo S. Sugano :
Development of versatile non-homologous end joining-based knock-in module for genome editing.,
Scientific Reports, Vol.8, No.1, 593, 2018.

(要約): CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering. An important aspect of genome engineering is efficient knock-in technology. For improved knock-in efficiency, the non-homologous end joining (NHEJ) repair pathway has been used over the homology-dependent repair pathway, but there remains a need to reduce the complexity of the preparation of donor vectors. We developed the versatile NHEJ-based knock-in module for genome editing (VIKING). Using the consensus sequence of the time-honored pUC vector to cut donor vectors, any vector with a pUC backbone could be used as the donor vector without customization. Conditions required to minimize random integration rates of the donor vector were also investigated. We attempted to isolate null lines of the VDR gene in human HaCaT keratinocytes using knock-in/knock-out with a selection marker cassette, and found 75% of clones isolated were successfully knocked-in. Although HaCaT cells have hypotetraploid genome composition, the results suggest multiple clones have VDR null phenotypes. VIKING modules enabled highly efficient knock-in of any vectors harboring pUC vectors. Users now can insert various existing vectors into an arbitrary locus in the genome. VIKING will contribute to low-cost genome engineering.
(徳島大学機関リポジトリ): ● Metadata: 112400
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-017-18911-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29330493; ● Summary page in Scopus @ Elsevier: 2-s2.0-85043529637

(徳島大学機関リポジトリ: 112400, DOI: 10.1038/s41598-017-18911-9, PubMed: 29330493, Elsevier: Scopus) Saya Ito, Sally Fujiyama-Nakamura, Shuhei Kimura, Jinseon Lim, Yuki Kamoshida, Yumi Shiozaki-Sato, Shun Sawatsubashi, Eriko Suzuki, Masahiko Tanabe, Takashi Ueda, Takuya Murata, Hiromi Kato, Fumiaki Ohtake, Ryoji Fujiki, Tsuneharu Miki, Alexander Kouzmenko, Ken-Ichi Takeyama and Shigeaki Kato :
Epigenetic silencing of core histone genes by HERS in Drosophila.,
Molecular Cell, Vol.45, No.4, 494-504, 2012.

(要約): Cell cycle-dependent expression of canonical histone proteins enables newly synthesized DNA to be integrated into chromatin in replicating cells. However, the molecular basis of cell cycle-dependency in the switching of histone gene regulation remains to be uncovered. Here, we report the identification and biochemical characterization of a molecular switcher, HERS (histone gene-specific epigenetic repressor in late S phase), for nucleosomal core histone gene inactivation in Drosophila. HERS protein is phosphorylated by a cyclin-dependent kinase (Cdk) at the end of S-phase. Phosphorylated HERS binds to histone gene regulatory regions and anchors HP1 and Su(var)3-9 to induce chromatin inactivation through histone H3 lysine 9 methylation. These findings illustrate a salient molecular switch linking epigenetic gene silencing to cell cycle-dependent histone production.
(キーワード): Animals / Cell Cycle / Drosophila / Drosophila Proteins / Epigenesis, Genetic / Gene Expression Regulation / Gene Silencing / Histones / Phosphorylation / Promoter Regions, Genetic / Repressor Proteins / S Phase
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.molcel.2011.12.029
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22365829; ● Search Scopus @ Elsevier (PMID): 22365829; ● Search Scopus @ Elsevier (DOI): 10.1016/j.molcel.2011.12.029

(DOI: 10.1016/j.molcel.2011.12.029, PubMed: 22365829) Shun Sawatsubashi, Takuya Murata, Jinseon Lim, Ryoji Fujiki, Saya Ito, Eriko Suzuki, Masahiko Tanabe, Yue Zhao, Shuhei Kimura, Sally Fujiyama, Takashi Ueda, Daiki Umetsu, Takashi Ito, Ken-ichi Takeyama and Shigeaki Kato :
A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor.,
Genes & Development, Vol.24, No.2, 159-170, 2009.

(要約): Chromatin reorganization is essential for transcriptional control by sequence-specific transcription factors. However, the molecular link between transcriptional control and chromatin reconfiguration remains unclear. By colocalization of the nuclear ecdysone receptor (EcR) on the ecdysone-induced puff in the salivary gland, Drosophila DEK (dDEK) was genetically identified as a coactivator of EcR in both insect cells and intact flies. Biochemical purification and characterization of the complexes containing fly and human DEKs revealed that DEKs serve as histone chaperones via phosphorylation by forming complexes with casein kinase 2. Consistent with the preferential association of the DEK complex with histones enriched in active epigenetic marks, dDEK facilitated H3.3 assembly during puff formation. In some human myeloid leukemia patients, DEK was fused to CAN by chromosomal translocation. This mutation significantly reduced formation of the DEK complex, which is required for histone chaperone activity. Thus, the present study suggests that at least one histone chaperone can be categorized as a type of transcriptional coactivator for nuclear receptors.
(キーワード): Animals / Chromatin / Chromosomal Proteins, Non-Histone / Conserved Sequence / Drosophila Proteins / Drosophila melanogaster / Ecdysone / Evolution, Molecular / Histone Chaperones / Humans / Leukemia, Myeloid, Acute / Nucleosomes / Oncogene Proteins / Poly-ADP-Ribose Binding Proteins / Receptors, Cytoplasmic and Nuclear / Receptors, Eph Family / Transcriptional Activation
(出版サイトへのリンク): ● Publication site (DOI): 10.1101/gad.1857410
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20040570; ● Search Scopus @ Elsevier (PMID): 20040570; ● Search Scopus @ Elsevier (DOI): 10.1101/gad.1857410

(DOI: 10.1101/gad.1857410, PubMed: 20040570) Sally Fujiyama-Nakamura, Saya Ito, Shun Sawatsubashi, Yoshio Yamauchi, Eriko Suzuki, Masahiko Tanabe, Shuhei Kimura, Takuya Murata, Toshiaki Isobe, Ken-ichi Takeyama and Shigeaki Kato :
BTB protein, dKLHL18/CG3571, serves as an adaptor subunit for a dCul3 ubiquitin ligase complex.,
Genes to Cells, Vol.14, No.8, 965-973, 2009.

(要約): The BTB domain is a highly conserved protein-protein interaction motif and functions in diverse cellular processes, including transcriptional regulation, ion channel assembly, cytoskeleton dynamics and apoptosis. Recently, it was reported that some BTB domain-containing proteins associate with Cullin-3 (Cul3), an E3 ubiquitin ligase, and act as an adaptor for Cul3 recognition of its substrate. However, the target substrates for the Cul3/BTB protein E3 ubiquitin ligase complex are largely unknown. Here, we report the characterization of a novel Drosophila BTB protein, dKLHL18/CG3571. By purification of a dKLHL18-associated complex, we identified CG10324, CG5808, l(2)37Cb and dCul3/guftagu. Indeed, the physical association of dKLHL18 with these proteins was observed in insect S2 cells, and genetic interactions among the identified factors were also observed in thorax development. Moreover, transient overexpression of dKLHL18 increased the ubiquitinated protein levels of CG10324 and CG5808. These findings suggest that dKLHL18 is an adaptor for a dCul3 E3 ubiquitin ligase to accommodate CG10324, CG5808 and l(2)37Cb proteins for ubiquitination.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / Cells, Cultured / Cullin Proteins / Drosophila Proteins / Drosophila melanogaster / Gene Expression Regulation, Developmental / Humans / Protein Interaction Domains and Motifs / Thorax / Ubiquitin
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/j.1365-2443.2009.01323.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19624754; ● Search Scopus @ Elsevier (PMID): 19624754; ● Search Scopus @ Elsevier (DOI): 10.1111/j.1365-2443.2009.01323.x

(DOI: 10.1111/j.1365-2443.2009.01323.x, PubMed: 19624754) Eriko Suzuki, Yue Zhao, Saya Ito, Shun Sawatsubashi, Takuya Murata, Takashi Furutani, Yuko Shirode, Kaoru Yamagata, Masahiko Tanabe, Shuhei Kimura, Takashi Ueda, Sally Fujiyama, Jinseon Lim, Hiroyuki Matsukawa, P Alexander Kouzmenko, Toshiro Aigaki, Tetsuya Tabata, Ken-ichi Takeyama and Shigeaki Kato :
Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity.,
Proceedings of the National Academy of Sciences of the United States of America, Vol.106, No.10, 3818-3822, 2009.

(要約): Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder caused by a polyglutamine repeat (polyQ) expansion within the human androgen receptor (AR). Unlike other neurodegenerative diseases caused by abnormal polyQ expansion, the onset of SBMA depends on androgen binding to mutant human polyQ-AR proteins. This is also observed in Drosophila eyes ectopically expressing the polyQ-AR mutants. We have genetically screened mediators of androgen-induced neurodegeneration caused by polyQ-AR mutants in Drosophila eyes. We identified Rbf (Retinoblastoma-family protein), the Drosophila homologue of human Rb (Retinoblastoma protein), as a neuroprotective factor. Androgen-dependent association of Rbf or Rb with AR was remarkably potentiated by aberrant polyQ expansion. Such potentiated Rb association appeared to attenuate recruitment of histone deacetyltransferase 1 (HDAC1), a corepressor of E2F function. Either overexpression of Rbf or E2F deficiency in fly eyes reduced the neurotoxicity of the polyQ-AR mutants. Induction of E2F function by polyQ-AR-bound androgen was suppressed by Rb in human neuroblastoma cells. We conclude that abnormal expansion of polyQ may potentiate innate androgen-dependent association of AR with Rb. This appears to lead to androgen-dependent onset of SBMA through aberrant E2F transactivation caused by suppressed histone deacetylation.
(キーワード): Androgens / Animals / Drosophila Proteins / Drosophila melanogaster / E2F Transcription Factors / Humans / Ligands / Muscular Atrophy, Spinal / Mutant Proteins / Nerve Degeneration / Peptides / Protein Binding / Receptors, Androgen / Retinoblastoma Protein / Transcription Factors / Transcriptional Activation
(出版サイトへのリンク): ● Publication site (DOI): 10.1073/pnas.0809819106
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19237573; ● Search Scopus @ Elsevier (PMID): 19237573; ● Search Scopus @ Elsevier (DOI): 10.1073/pnas.0809819106

(DOI: 10.1073/pnas.0809819106, PubMed: 19237573) Yue Zhao, Ken-ichi Takeyama, Shun Sawatsubashi, Saya Ito, Eriko Suzuki, Kaoru Yamagata, Masahiko Tanabe, Shuhei Kimura, Sally Fujiyama, Takashi Ueda, Takuya Murata, Hiroyuki Matsukawa, Yuko Shirode, P Alexander Kouzmenko, Feng Li, Testuya Tabata and Shigeaki Kato :
Corepressive action of CBP on androgen receptor transactivation in pericentric heterochromatin in a Drosophila experimental model system.,
Molecular and Cellular Biology, Vol.29, No.4, 1017-1034, 2008.

(要約): Ligand-bound nuclear receptors (NR) activate transcription of the target genes. This activation is coupled with histone modifications and chromatin remodeling through the function of various coregulators. However, the nature of the dependence of a NR coregulator action on the presence of the chromatin environment at the target genes is unclear. To address this issue, we have developed a modified position effect variegation experimental model system that includes an androgen-dependent reporter transgene inserted into either a pericentric heterochromatin region or a euchromatic region of Drosophila chromosome. Human androgen receptor (AR) and its constitutively active truncation mutant (AR AF-1) were transcriptionally functional in both chromosomal regions. Predictably, the level of AR-induced transactivation was lower in the pericentric heterochromatin. In genetic screening for AR AF-1 coregulators, Drosophila CREB binding protein (dCBP) was found to corepress AR transactivation at the pericentric region whereas it led to coactivation in the euchromatic area. Mutations of Sir2 acetylation sites or deletion of the CBP acetyltransferase domain abrogated dCBP corepressive action for AR at heterochromatic areas in vivo. Such a CBP corepressor function for AR was observed in the transcriptionally silent promoter of an AR target gene in cultured mammalian cells. Thus, our findings suggest that the action of NR coregulators may depend on the state of chromatin at the target loci.
(キーワード): Acetylation / Amino Acid Sequence / Animals / CREB-Binding Protein / Catalytic Domain / Cell Line, Tumor / Chromosomal Position Effects / Conserved Sequence / Drosophila Proteins / Drosophila melanogaster / Euchromatin / Heterochromatin / Histone Deacetylases / Histones / Humans / Lysine / Methylation / Models, Genetic / Molecular Sequence Data / Promoter Regions, Genetic / Receptors, Androgen / Repressor Proteins / Sirtuins / Transcriptional Activation
(出版サイトへのリンク): ● Publication site (DOI): 10.1128/MCB.02123-07
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19075001; ● Search Scopus @ Elsevier (PMID): 19075001; ● Search Scopus @ Elsevier (DOI): 10.1128/MCB.02123-07

(DOI: 10.1128/MCB.02123-07, PubMed: 19075001) Takuya Murata, Eriko Suzuki, Saya Ito, Shun Sawatsubashi, Yue Zhao, Kaoru Yamagata, Masahiko Tanabe, Sally Fujiyama, Shuhei Kimura, Takashi Ueda, Hiroyuki Matsukawa, Alexander Kouzmenko, Takashi Furutani, Erina Kuranaga, Masayuki Miura, Ken-ichi Takeyama and Shigeaki Kato :
RNA-binding protein hoip accelerates polyQ-induced neurodegeneration in Drosophila.,
Bioscience, Biotechnology, and Biochemistry, Vol.72, No.9, 2255-2261, 2008.

(要約): Abnormal polyglutamine (polyQ) expansion in the N-terminal domain of the human androgen receptor (hAR) is known to cause spinobulbar muscular atrophy (SBMA), a hereditary human neurodegenerative disorder. To explore the molecular mechanisms of neurodegeneration in SBMA, we genetically screened modulators of neurodegeneration in a Drosophila SBMA experimental model system. We identified hoip as an accelerator of polyQ-induced neurodegeneration. We found that hoip forms a complex with 18s rRNA together nop56 and nop5 proteins, whose human homologs are known to form a snoRNP complex involved in ribosomal RNA processing. Significantly, the levels of mutant polyQ-hAR were up-regulated in a mutant line overexpressing hoip. Consistently, severe neurodegeneration phenotype (rough eye) was also observed in both nop56 and nop5 overexpression mutant lines. These findings suggest that the process of neurodegeneration induced by abnormal polyQ expansion in the hAR may be regulated by the activity of snoRNP complex.
(キーワード): Animals / Animals, Genetically Modified / Cells, Cultured / Disease Models, Animal / Drosophila / Drosophila Proteins / Eye / Genes, Insect / Muscular Disorders, Atrophic / Mutation / Nerve Degeneration / Peptides / RNA-Binding Proteins / Receptors, Androgen / Transfection
(出版サイトへのリンク): ● Publication site (DOI): 10.1271/bbb.70829
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18776683; ● Search Scopus @ Elsevier (PMID): 18776683; ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.70829

(DOI: 10.1271/bbb.70829, PubMed: 18776683) Shuhei Kimura, Shun Sawatsubashi, Saya Ito, Alexander Kouzmenko, Eriko Suzuki, Yue Zhao, Kaoru Yamagata, Masahiko Tanabe, Takashi Ueda, Sari Fujiyama, Takuya Murata, Hiroyuki Matsukawa, Ken-Ichi Takeyama, Nobuo Yaegashi and Shigeaki Kato :
Drosophila arginine methyltransferase 1 (DART1) is an ecdysone receptor co-repressor.,
Biochemical and Biophysical Research Communications, Vol.371, No.4, 889-893, 2008.

(要約): Histone arginine methylation is an epigenetic marker that regulates gene expression by defining the chromatin state. Arginine methyltransferases, therefore, serve as transcriptional co-regulators. However, unlike other transcriptional co-regulators, the physiological roles of arginine methyltransferases are poorly understood. Drosophila arginine methyltransferase 1 (DART1), the mammalian PRMT1 homologue, methylates the arginine residue of histone H4 (H4R3me2). Disruption of DART1 in Drosophila by imprecise P-element excision resulted in low viability during metamorphosis in the pupal stages. In the pupal stage, an ecdysone hormone signal is critical for developmental progression. DART1 interacted with the nuclear ecdysone receptor (EcR) in a ligand-dependent manner, and co-repressed EcR in intact flies. These findings suggest that DART1, a histone arginine methyltransferase, is a co-repressor of EcR that is indispensable for normal pupal development in the intact fly.
(キーワード): Animals / Drosophila Proteins / Drosophila melanogaster / Genes, Lethal / Histones / Immunoprecipitation / Methylation / Methyltransferases / Mutation / Receptors, Steroid / Repressor Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2008.05.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18468516; ● Search Scopus @ Elsevier (PMID): 18468516; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2008.05.003

(DOI: 10.1016/j.bbrc.2008.05.003, PubMed: 18468516) Yue Zhao, Guillaume Lang, Saya Ito, Jacques Bonnet, Eric Metzger, Shun Sawatsubashi, Eriko Suzuki, Xavier Guezennec Le, G Hendrik Stunnenberg, Aleksey Krasnov, G Sofia Georgieva, Roland Schüle, Ken-Ichi Takeyama, Shigeaki Kato, László Tora and Didier Devys :
A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing.,
Molecular Cell, Vol.29, No.1, 92-101, 2008.

(要約): Transcriptional activators, several different coactivators, and general transcription factors are necessary to access specific loci in the dense chromatin structure to allow precise initiation of RNA polymerase II (Pol II) transcription. Histone acetyltransferase (HAT) complexes were implicated in loosening the chromatin around promoters and thus in gene activation. Here we demonstrate that the 2 MDa GCN5 HAT-containing metazoan TFTC/STAGA complexes contain a histone H2A and H2B deubiquitinase activity. We have identified three additional subunits of TFTC/STAGA (ATXN7L3, USP22, and ENY2) that form the deubiquitination module. Importantly, we found that this module is an enhancer of position effect variegation in Drosophila. Furthermore, we demonstrate that ATXN7L3, USP22, and ENY2 are required as cofactors for the full transcriptional activity by nuclear receptors. Thus, the deubiquitinase activity of the TFTC/STAGA HAT complex is necessary to counteract heterochromatin silencing and acts as a positive cofactor for activation by nuclear receptors in vivo.
(キーワード): Amino Acid Sequence / Animals / Animals, Genetically Modified / Cell Line / Conserved Sequence / Drosophila Proteins / Drosophila melanogaster / Endopeptidases / Gene Silencing / Heterochromatin / Histone Acetyltransferases / Humans / Molecular Sequence Data / Multiprotein Complexes / Promoter Regions, Genetic / Protein Interaction Mapping / RNA Polymerase II / Receptors, Androgen / Recombinant Fusion Proteins / Sequence Alignment / Sequence Homology, Amino Acid / Thiolester Hydrolases / Trans-Activators / Transcription Factors / Transcription Factors, General / Transcription, Genetic / Ubiquitination / p300-CBP Transcription Factors
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.molcel.2007.12.011
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18206972; ● Search Scopus @ Elsevier (PMID): 18206972; ● Search Scopus @ Elsevier (DOI): 10.1016/j.molcel.2007.12.011

(DOI: 10.1016/j.molcel.2007.12.011, PubMed: 18206972) P Alexander Kouzmenko, Ken-Ichi Takeyama, Saya Ito, Takashi Furutani, Shun Sawatsubashi, Akio Maki, Eriko Suzuki, Yoshihiro Kawasaki, Tetsu Akiyama, Testuya Tabata and Shigeaki Kato :
Wnt/beta-catenin and estrogen signaling converge in vivo.,
The Journal of Biological Chemistry, Vol.279, No.39, 40255-40258, 2004.

(要約): Wnt and estrogen signaling represent important regulatory pathways, each controlling a wide range of biological processes. While an increasing number of observations suggest potential convergence between these pathways, no direct evidence of their functional interaction has been reported. Using human colon and breast cancer cells, we found that estrogen receptor (ER) alpha- and beta-catenin precipitated within the same immunocomplexes, reciprocally enhanced the transactivation of cognate reporter genes, and were reciprocally recruited to cognate response elements in the promoters of endogenous target genes. Using transgenic Drosophila that ectopically expressed human ERalpha alone or together with metabolically stable beta-catenin/Armadillo mutants, we demonstrated genetic interaction between these signal transducers in vivo. Thus, we present here the first direct evidence of cross-talk between Wnt and estrogen signaling pathways via functional interaction between beta-catenin and ERalpha.
(キーワード): Animals / Apoptosis / Cell Line, Tumor / Chromatin / Cytoskeletal Proteins / Drosophila / Estrogen Receptor alpha / Estrogens / Genes, Reporter / Humans / Immunoblotting / In Situ Nick-End Labeling / Mutation / Precipitin Tests / Promoter Regions, Genetic / Protein Binding / Receptors, Estrogen / Signal Transduction / Trans-Activators / Transcription, Genetic / Transcriptional Activation / Transfection / Transgenes / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1074/jbc.C400331200
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15304487; ● Search Scopus @ Elsevier (PMID): 15304487; ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.C400331200

(DOI: 10.1074/jbc.C400331200, PubMed: 15304487) Akio Maki, Shun Sawatsubashi, Saya Ito, Yuko Shirode, Eriko Suzuki, Yue Zhao, Kaoru Yamagata, Alexander Kouzmenko, Ken-Ichi Takeyama and Shigeaki Kato :
Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers.,
Biochemical and Biophysical Research Communications, Vol.320, No.1, 262-267, 2004.

(要約): Insect development is controlled by the combined actions of ecdysteroid and juvenile hormones. Transcriptional control by ecdysteroid hormones is mediated via two nuclear receptor superfamily members, ecdysone receptor (EcR) and its heterodimeric partner, ultraspiracle (USP). Although the ecdysteroid hormone 20-hydroxyecdysone acts as an EcR ligand and activates transcription through EcR/USP heterodimers, the activity of juvenile hormones, such as Juvenile hormone III (JH III), and methoprenic acid (MA) via USP remains unclear. Here, we demonstrate that juvenile hormones act as USP ligands and exhibit suppressive effects on ecdysone-dependent EcR transactivation. JH III- and MA-bound USP markedly repressed ecdysone-dependent EcR transactivation through shifting of the USP ligand-binding domain alpha-helix 12 without affecting EcR/USP heterodimerization or DNA binding. Moreover, transcriptional repression by USP ligands was attenuated by a histone deacetylation inhibitor. Our results suggested that juvenile hormones serve as USP ligands that antagonize EcR-mediated ecdysone actions through the recruitment of histone deacetylase complexes.
(キーワード): Animals / Cell Line / DNA-Binding Proteins / Dimerization / Drosophila Proteins / Drosophila melanogaster / Protein Binding / Receptors, Steroid / Repressor Proteins / Sesquiterpenes / Transcription Factors / Transcriptional Activation
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2004.05.156
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15207730; ● Search Scopus @ Elsevier (PMID): 15207730; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2004.05.156

(DOI: 10.1016/j.bbrc.2004.05.156, PubMed: 15207730) Shun Sawatsubashi, Akio Maki, Saya Ito, Yuko Shirode, Eriko Suzuki, Yue Zhao, Kaoru Yamagata, Alexander Kouzmenko, Ken-Ichi Takeyama and Shigeaki Kato :
Ecdysone receptor-dependent gene regulation mediates histone poly(ADP-ribosyl)ation.,
Biochemical and Biophysical Research Communications, Vol.320, No.1, 268-272, 2004.

(要約): While the ecdysone dependency of puff formation in giant polytene chromosomes from fly salivary glands has been well documented, the molecular mechanisms underlying this process remain unknown. However, it does appear to involve chromatin remodeling and modification mediated by ecdysone receptor (EcR). As Drosophila poly(ADP-ribose) polymerase (dPARP) has recently been reported to be involved in ecdysone-induced puff formation, we decided to test the possible role of dPARP in ligand-induced dEcR transactivation in an insect system. dPARP co-activated the ligand-induced transactivation function of EcR in the insect cell line S2, and appeared to physically interact with EcR in a ligand-dependent manner. ChIP analysis of an EcR target gene promoter revealed ligand-dependent recruitment of dPARP with poly(ADP-ribosyl)ation of histones in the EcR binding site and, surprisingly, also in a distal region of the promoter. Our results indicated that EcR-mediated gene regulation may be coupled with chromatin modification through poly(ADP-ribosyl)ation.
(キーワード): Animals / Cell Line / Drosophila melanogaster / Gene Expression Regulation / Histones / Poly(ADP-ribose) Polymerases / Receptors, Steroid
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2004.05.157
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15207731; ● Search Scopus @ Elsevier (PMID): 15207731; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2004.05.157

(DOI: 10.1016/j.bbrc.2004.05.157, PubMed: 15207731) Akinori Ishihara, Shun Sawatsubashi and Kiyoshi Yamauchi :
Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors.,
Molecular and Cellular Endocrinology, Vol.199, No.1-2, 105-117, 2003.

(要約): We examined the effects of industrial, medical and agricultural chemicals on 3,5,3'-L-[125I]triiodothyronine ([125I]T(3)) binding to transthyretins (TTRs) and thyroid hormone receptors (TRs). Among the chemicals investigated diethylstilbestrol (DES) was the most powerful inhibitor of [125I]T(3) binding to chicken and bullfrog TTR (cTTR and bTTR). Inhibition of [125I]T(3) binding was more apparent in cTTR than bTTR. Scatchard analysis revealed DES, pentachlorophenol and ioxynil as competitive inhibitors of [125I]T(3) binding to cTTR and bTTR. However, cTTR's affinity for the three chemicals was higher than its affinity for T(3). A miticide dicofol (10(-10)-10(-7) M) activated [125I]T(3) binding to bTTR up to 170%. However, at 4x10(-5) M it inhibited [125I]T(3) binding by 83%. Dicofol's biphasic effect upon [125I]T(3) binding was not detected in TTRs from other species. DES and pentachlorophenol, in the presence of plasma, increased cellular uptake of [125I]T(3) in vitro, by displacing [125I]T(3) from its plasma binding sites. These chemicals did not, however, affect the association of cTTR with chicken retinol-binding protein. All chemicals investigated had little or no influence on [125I]T(3) binding to chicken TR (cTR) and bullfrog TR (bTR). Several endocrine disrupting chemicals that were tested interfered with T(3) binding to TTR rather than to TR. Binding of the endocrine disrupting chemicals to TTR may weaken their intrinsic effects on target cells by depressing their free concentrations in plasma. However, this may affect TH homeostasis in vivo by altering the free concentrations of plasma THs.
(キーワード): Animals / Binding, Competitive / Carrier Proteins / Chickens / Endocrine System / Erythrocytes / Humans / Iodine Radioisotopes / Membrane Proteins / Organic Chemicals / Prealbumin / Protein Binding / Rana catesbeiana / Receptors, Thyroid Hormone / Salmon / Thyroid Hormones / Triiodothyronine
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0303-7207(02)00302-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12581883; ● Search Scopus @ Elsevier (PMID): 12581883; ● Search Scopus @ Elsevier (DOI): 10.1016/S0303-7207(02)00302-7

(DOI: 10.1016/S0303-7207(02)00302-7, PubMed: 12581883) N Nishiyama, Shun Sawatsubashi, M Ishida and K Yamauchi :
Organization and expression of the Paramecium caudatum gene encoding nucleosome assembly protein 1.,
Gene, Vol.280, No.1-2, 107-114, 2001.

(要約): The complete genomic and partial complementary DNAs encoding the ciliate Paramecium caudatum nucleosome assembly protein 1 (NAP1) have been sequenced. The nap1 gene is situated 1.2 kbp from the hemoglobin (hb) gene, with the 3' end of both genes facing each other. The nap1 gene contains no introns, and encodes a protein of 369 amino acid residues with a calculated molecular weight of 42,627. The P. caudatum NAP1 amino acid sequence shares only 23-27% identity with NAP1 amino acid sequences from other eukaryotes. Although the nap1 transcript was detected in the P. caudatum cells at both the logarithmic and stationary phases, its level increased during the stationary phase. Southern blot analysis and polymerase chain reaction amplification revealed that the P. caudatum macronucleus has a heterogeneous composition at genomic regions around the nap1 gene. The present studies indicate the nap1 and hb genes are closely arranged in the macronucleus with the intergenic region between their sequences heterogeneously composed.
(キーワード): Amino Acid Sequence / Animals / Blotting, Northern / Cell Cycle Proteins / DNA, Complementary / DNA, Protozoan / Gene Expression / Genes, Protozoan / Hemoglobins / Molecular Sequence Data / Nuclear Proteins / Nucleosome Assembly Protein 1 / Paramecium / Phylogeny / Proteins / RNA, Messenger / Sequence Alignment / Sequence Analysis, DNA / Sequence Homology, Amino Acid
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11738823; ● Search Scopus @ Elsevier (PMID): 11738823

(PubMed: 11738823)

MISC

研究者総覧に該当データはありませんでした。

総説・解説

沢津橋俊 :
[Update on recent progress in vitamin D research. Vitamin D in the treatment of psoriasis.],
Clinical Calcium, Vol.27, No.11, 1629-1635, 2017年11月.

(要約): Active vitamin D and analogs exert immunomodulatory effects and potent effects on cellular differentiation and proliferation in the skin. In the last few decades, it has convincingly been shown that these analogs are effective and safe in the topical treatment of psoriasis, where they nowadays represent a standard therapy. However, the mechanism of vitamin D action in the treatment of psoriasis remains largely unknown. Here, we reviewed and discussed the recent findings of molecular action of vitamin D in psoriasis.
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29074837; ● Search Scopus @ Elsevier (PMID): 29074837

(PubMed: 29074837) 沢津橋俊 :
[Hair follicle stem cells.],
Clinical Calcium, Vol.27, No.6, 803-808, 2017年6月.

(要約): The hair follicle is a complex miniorgan of the skin and undergoes cycles of growth(anagen), apoptosis-mediated regression(catagen)and rest(telogen). Regeneration of the new hair shaft dependent on the activation of hair follicle stem cells(HFSCs), harboured in the bulge region. Using a hair follicle model, some molecular players that control the balance between HFSC maintenance and ageing-associated HFSC dysfunction have been identified. Here, we reviewed and discussed the recent findings of molecular characterization of HFSCs biology and pathology.
(キーワード): Animals / Cell Differentiation / Cellular Microenvironment / Cellular Senescence / Hair Follicle / Humans / Stem Cells
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28536317; ● Search Scopus @ Elsevier (PMID): 28536317

(PubMed: 28536317) 沢津橋俊 :
[Bone and Nutrition. The vitamin D functions in osteoblasts and osteocytes].,
Clinical Calcium, Vol.25, No.7, 991-997, 2015年7月.

(要約): The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25 (OH) (2)D(3)), plays a key role in mineral and bone homeostasis. 1,25 (OH) (2)D(3), through binding to the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, regulates the expression of many genes in osteoblasts and osteocytes. The VDR functions in a largely 1,25 (OH) (2)D(3)-controlled manner by interacting directly with vitamin D response elements located within regulatory regions that are linked to cell-specific target genes. However, the mechanism of VDR action on these bone cell types remains largely unknown. While the direct actions of 1,25 (OH) (2)D(3) on bone cells are complex and include both cell autonomous and paracrine mechanisms. In this review, we discuss how the VDR affects the transcriptional response of these cells and contribute to bone homeostasis.
(キーワード): Animals / Autocrine Communication / Calcification, Physiologic / Homeostasis / Humans / Mice / Osteoblasts / Osteocytes / Paracrine Communication / Protein Binding / Receptors, Calcitriol / Transcription Factors / Vitamin D
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26119311; ● Search Scopus @ Elsevier (PMID): 26119311

(PubMed: 26119311) 沢津橋俊 :
[Current Topics on Vitamin D. The vitamin D functions in keratinocytes and its therapeutic applications].,
Clinical Calcium, Vol.25, No.3, 367-371, 2015年3月.

(要約): 1,25 (OH) 2D and calcium have been shown to promote epidermal keratinocyte differentiation and prevent proliferation. These prodifferentiation and antiproliferative effects of 1,25 (OH) 2D have led to its clinical use in the treatment of psoriasis. However, the mechanism of vitamin D action on keratinocytes remains largely unknown. While the actions of calcium and the vitamin D receptor signaling pathways on epidermal keratinocyte differentiation are redundant, their effects on the hair follicle are not. In this review, we discuss how the vitamin D and its receptor contribute to skin and hair follicle homeostasis.
(キーワード): Animals / Calcium / Cell Differentiation / Hair / Humans / Keratinocytes / Skin / Vitamin D
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25716809; ● Search Scopus @ Elsevier (PMID): 25716809

(PubMed: 25716809)

講演・発表

Yuichi Takashi, Yuka Kinoshita, Nobuaki Ito, Shun Sawatsubashi, Hidetaka Kosako, Masahiro Abe, Munehide Matsuhisa, Toshio Matsumoto and Seiji Fukumoto :
FGF receptor 1c works as a phosphate-sensor to regulate FGF23 production,
ASBMR 2018 Annual Meeting Registration Confirmation, Sep. 2018. 加藤茂明, 金本義明, 早川哲, 澤田崇広, 沢津橋俊, 福本誠二, 森甚一 :
カルシウム代謝調整因子群によるCYP24A1転写制御,
ビタミン, Vol.96, No.8, 376-377, 2022年8月. 沢津橋俊, 池戸葵, 松本俊夫, 今井祐記, 福本誠二 :
ヒト疾患型点変異を導入したビタミンD依存性くる病/骨軟化症モデルマウスの機能解析,
日本骨代謝学会学術集会プログラム抄録集, Vol.40, 119, 2022年7月. 金本義明, 西村耕一, 澤田崇広, 早川哲, 黒川友博, 沢津橋俊, 森甚一, 加藤茂明 :
新規ヒトビタミンD標的non-coding RNA遺伝子群の同定,
日本骨代謝学会学術集会プログラム抄録集, Vol.40, 152, 2022年7月. 金本義明, 沢津橋俊, 福本誠二, 加藤茂明 :
カルシウム代謝調整因子群によるCYP24A1転写制御,
日本骨代謝学会学術集会プログラム抄録集, Vol.40, 119, 2022年7月. 横山敦, 纐纈拓海, 尾坪優李, 沢津橋俊, 島弘季, 佐藤郁郎, 川村貞文, 鈴木貴, 五十嵐和彦, 菅原明 :
核内受容体新規転写共役因子の探索,
日本アンドロロジー学会総会記事, Vol.41, 55, 2022年5月. 横山敦, 纐纈拓海, 尾坪優李, 沢津橋俊, 島弘季, 佐藤郁郎, 川村貞文, 鈴木貴, 五十嵐和彦, 菅原明 :
アンドロゲン受容体新規転写共役因子の探索,
日本アンドロロジー学会総会記事, Vol.41, 83, 2022年5月. 金本義明, 西村耕一, 澤田崇広, 早川哲, 黒川友博, 沢津橋俊, 森甚一, 加藤茂明 :
新規ヒトビタミンD標的non-coding RNA遺伝子群の同定,
日本栄養・食糧学会大会講演要旨集, Vol.76, 251, 2022年5月. 金本義明, 早川哲, 澤田崇広, 沢津橋俊, 福本誠二, 森甚一, 加藤茂明 :
カルシウム代謝調整因子群によるCYP24A1転写制御,
日本栄養・食糧学会大会講演要旨集, Vol.76, 251, 2022年5月. 金本義明, 西村耕一, 澤田崇広, 早川哲, 黒川友博, 沢津橋俊, 森甚一, 加藤茂明 :
新規ヒトビタミンD標的non-coding RNA遺伝子群の同定,
ビタミン, Vol.96, No.4, 192, 2022年4月. 沢津橋俊, 貝沼梨沙, 松本俊夫, 福本誠二 :
栄養代謝状態が調節するグルココルチコイド受容体の転写制御機構の解明,
日本内分泌学会雑誌, Vol.97, No.1, 271, 2021年4月. 沢津橋俊, 西村耕一, 松本俊夫, 福本誠二 :
ヒストンシャペロンDEKによる核内構造体形成メカニズムの解明,
日本生化学会大会(Web), Vol.94, 554, 2021年. 西村耕一, 沢津橋俊, 松本俊夫, 福本誠二 :
SWI/SNF複合体のIDRによる相分離を介した核内受容体AF-1領域との相互作用解析,
日本生化学会大会(Web), Vol.94, 643, 2021年. 沢津橋俊, 松本俊夫, 福本誠二 :
栄養情報が調節するグルココルチコイド受容体の転写制御機構の解析,
第93回日本内分泌学会学術総会, Vol.96, No.1, 238, 2020年7月. 髙士祐一, 沢津橋俊, 遠藤逸朗, 安倍正博, 松久宗英, 松本俊夫, 福本誠二 :
FGFR1は血中FGF23濃度を制御するリン感知受容体である,
第38回日本骨代謝学会学術集会, 2019年10月. 髙士祐一, 小迫英尊, 沢津橋俊, Y Kinoshita, N Ito, 松久宗英, M Matsumoto, 福本誠二 :
FGF recepotor I works as a phosphate-sensor to regulate FGF23 production,
15th Bone Biology Forum, 2019年8月. 髙士祐一, 小迫英尊, 沢津橋俊, 木下祐加, 伊東伸朗, 安倍正博, 松久宗英, 加藤茂明, 松本俊夫, 福本誠二 :
FGFR1はFGF23濃度調節を媒介するリン感知受容体である,
第92回日本内分泌学会学術総会, Vol.95, No.1, 333, 2019年5月.

研究会・報告書: 沢津橋俊 :
疾患型点変異を導入したビタミンD依存性くる病/骨軟化症モデルマウスの機能解析,
日本レチノイド研究会, 2022年10月.

特許: 沢津橋俊, 菅野茂夫 : ゲノム編集方法, 特願2017-027384 (2017年2月), .
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: 毛包をモデルとした臓器・器官の恒常性維持機構とその破綻による病態の解明 (研究課題/領域番号: 24K10533 )
ゲノム多型に起因する疾患の発症プロセスの解明 (研究課題/領域番号: 22H02819 )
ファーストメッセンジャーとしてのリンの作用機序の解明 (研究課題/領域番号: 19H03676 )
Non-coding領域に存在する疾患原因SNPの同定と機能解析 (研究課題/領域番号: 18KT0024 )
ビタミンD依存性くる病モデルマウスから切り拓く毛周期破綻による脱毛機序の解明 (研究課題/領域番号: 18K19518 )
正常な皮膚機能に関わるビタミンD受容体の標的遺伝子探索とその発現機序の解明 (研究課題/領域番号: 16K19556 )
糖質応答転写因子ChREBPをターゲットとした糖尿病性腎症の新規治療法の開発 (研究課題/領域番号: 16K15492 )
骨―脂肪組織連関の制御に関わるIL-11の役割および作用機序の解明 (研究課題/領域番号: 16H05327 )
栄養情報を反映した新規グルココルチコイド作用切り換えメカニズムの解明 (研究課題/領域番号: 24591357 )
慢性炎症病態を制御するシグナル依存性エピゲノム制御メカニズムの解析 (研究課題/領域番号: 23117505 )
パフ局在化因子の分子遺伝学的探索を基盤とした活性化クロマチン構造調節機構の解明 (研究課題/領域番号: 22770166 )
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専門分野・研究分野: 分子生物学 (Molecular Biology)
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Jグローバル最終確認日: 2024/4/20 01:23
氏名（漢字）: 沢津橋俊
氏名（フリガナ）: サワツバシシュン
氏名（英字）: Sawatsubashi Shun
所属機関: 徳島大学准教授

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researchmap最終確認日: 2024/4/14 01:38
氏名（漢字）: 沢津橋俊
氏名（フリガナ）: サワツバシシュン
氏名（英字）: Sawatsubashi Shun
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登録日時: 2018/8/13 12:03
更新日時: 2024/3/1 10:11
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所属: 徳島大学
部署: 先端酵素学研究所
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学位授与機関: 東京大学
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研究者番号: 70535103

所属（現在）: 2024/4/1 : 徳島大学, 先端酵素学研究所, 准教授

所属（過去の研究課題 情報に基づく）*注記: 2023/4/1 – 2024/4/1 : 徳島大学, 先端酵素学研究所, 准教授
2020/4/1 – 2021/4/1 : 徳島大学, 先端酵素学研究所, 特任准教授
2016/4/1 – 2019/4/1 : 徳島大学, 先端酵素学研究所(オープンイノベ), 特任講師
2017/4/1 : 徳島大学, 藤井節郎記念医科学センター, 講師
2014/4/1 : 徳島大学, 藤井節郎記念医科学センター, 特任講師
2013/4/1 : 徳島大学, 藤井節郎記念医科学センター, 特任助教
2010/4/1 – 2012/4/1 : 群馬大学, 生体調節研究所, 助教

審査区分/研究分野

研究代表者

生物系 / 生物学 / 生物科学 / 分子生物学
生物系 / 医歯薬学 / 内科系臨床医学 / 内分泌学
生物系
中区分52:内科学一般およびその関連分野
小区分52010:内科学一般関連

研究代表者以外

生物系 / 医歯薬学 / 内科系臨床医学 / 代謝学
生物系 / 医歯薬学 / 内科系臨床医学 / 内分泌学
複雑系疾病論
小区分53040:腎臓内科学関連
小区分48040:医化学関連

キーワード

研究代表者

転写 / クロマチン / 核内受容体 / エクダイソン / エクダイソンレセプター / 転写制御 / グルココルチコイド / 翻訳後修飾 / エネルギー代謝 / O-GlcNAc / エピゲノム制御因子 / 炎症シグナル / エピゲノム制御 / ステロイドホルモン / グルココルチコイドレセプター / GR / O-GlcNAc修飾 / OGT / グルココルチコイド受容体 / O-GlcNAc転移酵素 / グルコース / リン酸化 / ビタミンD / ビタミンD受容体 / 皮膚 / 毛包 / S100A8 / 毛周期 / 乾癬 / 表皮 / 内分泌学 / くる病 / 脱毛 / ゲノム編集 / 退縮期 / ビタミンD依存性くる病 / 点変異

研究代表者以外

遺伝子 / シグナル伝達 / 脂質 / 老化 / 骨粗鬆症 / 骨代謝 / 骨・カルシウム代謝異常 / 骨代謝学 / 骨ー脂肪組織関連 / 骨－脂肪組織連関 / CRISPR/Cas9システム / ChREBP / 糖尿病性腎症 / ハイスループットスクリーニング / 化合物ライブラリー / 糖質応答転写因子 / 創薬 / スクリーニング / リン / 線維芽細胞増殖因子23 / 線維芽細胞増殖因子受容体 / 繊維芽細胞増殖因子受容体 / GWAS / 一塩基多型 / SNP / ChIP-seq / 転写因子 / Noncoding SNP

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2020年12月25日

治療法・予防法の開発を指向した老化を定量する技術の開発

髙岡勝吉沢津橋俊榊原伊織

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沢津橋 俊

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沢津橋俊