Faculty Profiles - MASUYAMA Hisashi

MISC - MASUYAMA Hisashi

Division display 481 - 496 of about 496 ／ All the affair displays >>

石田理, 平松祐司, 西井英, 中田高公, 増山寿, 水谷靖司, 上村茂仁, 工藤尚文

日本産科婦人科學會雜誌 50 "S - 220" 1998

伊藤裕徳, 上村茂仁, 国富衛, 増山寿, 水谷靖司, 平松祐司, 工藤尚文

日本産科婦人科學會雜誌 50 "S - 196" 1998

Evidence for ligand-dependent intramolecular folding of the AF-2 domain in vitamin D receptor-activated transcription and coactivator interaction

H Masuyama, CM Brownfield, R StArnaud, PN MacDonald

MOLECULAR ENDOCRINOLOGY 11 ( 10 ) 1507 - 1517 1997.9

Language：English Publisher：ENDOCRINE SOC

A ligand-dependent transcriptional activation domain (AF-2) exists in region E of the nuclear receptors. This highly conserved domain may contact several coactivators that are putatively involved in nuclear receptor-mediated transcription. In this study, a panel of vitamin D receptor (VDR) AF-2 mutants was created to examine the importance of several conserved residues in VDR-activated transcription. Two AF-2 mutants (L417S and E420Q) exhibited normal ligand binding, heterodimerization with retinoid X receptor, and vitamin D-responsive element interaction, but they were transcriptionally inactive in a VDR-responsive reporter gene assay. All AF-2 mutations that abolished VDR-mediated transactivation also eliminated interactions between VDR and several putative coactivator proteins including suppressor of gall (SUG1), steroid hormone receptor coactivator-1 (SRC-1), or receptor interacting protein (RIP140), suggesting that coactivator interaction is important for AF-5-mediated transcription. In support of this concept, the minimal AF-2 domain [VDR(408- 427] fused to the gal4 DNA binding domain was sufficient to mediate transactivation as well as interaction with putative coactivators. Introducing the L417S and E420Q mutations into the minimal AF-2 domain abolished this autonomous transactivation and coactivator interactions. Finally, we demonstrate that the minimal AF-2 domain interacted with an AF-2 deletion mutant of the VDR in a 1,25-(OH)(2)D-3-dependent manner, suggesting a ligand-induced intramolecular folding of the VDR AF-2 domain. The L417S mutant of this domain disrupted the interaction with VDR ligand-binding domain, while the E420Q mutant did not affect this interaction. These studies suggest that the conserved AF-2 motif may mediate transactivation through ligand-dependent intermolecular interaction with coactivators and through ligand-induced intramolecular contacts with the VDR ligand-binding domain itself.

DOI： 10.1210/me.11.10.1507

Web of Science

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The N-terminal domain of transcription factor IIB is required for direct interaction with the vitamin D receptor and participates in vitamin D-mediated transcription

H Masuyama, SC Jefcoat, PN MacDonald

MOLECULAR ENDOCRINOLOGY 11 ( 2 ) 218 - 228 1997.2

Language：English Publisher：ENDOCRINE SOC

The interaction of the vitamin D receptor (VDR) with transcription factor IIB (TFIIB) represents a potential physical link between the VDR-DNA complex and the transcription preinitiation complex. However, the functional relevance of the VDR-TFIIB interaction in vitamin D-mediated transcription is not well understood. In the present study, we used site-directed mutagenesis to demonstrate that the structural integrity of the amino-terminal zinc finger of TFIIB is essential for VDR-TFIIB complex formation. Altering the putative zinc-coordinating residues (C15, C34, C37, or H18) to serines abolished TFIIB interaction with the VDR as assessed in a yeast two-hybrid system and by in vitro protein interaction assays. This N-terminal, VDR-interactive domain functioned as a selective, dominant-negative inhibitor of vitamin D-mediated transcription. Expressing amino acids 1-124 of human TFIIB (N-TFIIB) in COS-7 cells or in osteoblastic ROS17/2.8 cells effectively suppressed 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3)-induced transcription, but had no effect on basal or glucocorticoid-activated transcription. A mutant N-terminal domain [N-TFIIB(C34S:C37S)] that does not interact with VDR had no impact on 1,25(OH)(2)D-3-induced transcription. Interestingly, both in vitro and in vivo protein interaction assays showed that the VDR-TFIIB protein complex was disrupted by the 1,25-(OH)(2)D-3 ligand. Mechanistically, these data establish a functional role for the N terminus of TFIIB in VDR-mediated transcription, and they allude to a role for unliganded VDR in targeting TFIIB to the promoter regions of vitamin D-responsive target genes.

DOI： 10.1210/me.11.2.218

Web of Science

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Effect of Epidermal Growth Factor on Rat Placental Amino Acid Transport and Regulation of Epidermal Growth Factor Expression in Rat Liver

H.Masuyama, Y.Hiramatsu, T.Kudo

J Perinat Med 1997

408 ポリアミン代謝阻害剤DL--α-Difluoromenthyl ornithine (DFMO)の胎児発育への影響

石田理, 平松祐司, 西井英, 中田高公, 伊原直美, 増山寿, 上村茂仁, 工藤尚文

日本産科婦人科學會雜誌 48 "S - 311" 1996