c-Ski acts as a transcriptional co-repressor in transforming growth factor-β signaling through interaction with Smads

被引:325
作者
Akiyoshi, S
Inoue, H
Hanai, J
Kusanagi, K
Nemoto, N
Miyazono, K
Kawabata, M
机构
[1] Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Toshima Ku, Tokyo 1708455, Japan
[2] Japan Soc Promot Sci, Res Future Program, Dept Biochem, Toshima Ku, Tokyo 1708455, Japan
[3] Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Dept Toxicol, Toyama 9300194, Japan
关键词
D O I
10.1074/jbc.274.49.35269
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Smads are intracellular signaling mediators of the transforming growth factor-beta (TGF-beta) superfamily that regulates a wide variety of biological processes. Among them, Smads 2 and 3 are activated specifically by TGF-beta. We identified c-Ski as a Smad2 interacting protein. c-Ski is the cellular homologue of the v-ski oncogene product and has been shown to repress transcription by recruiting histone deacetylase (HDAC). Smad2/3 interacts with c-Ski through its C-terminal MH2 domain in a TGF-beta-dependent manner. c-Ski contains two distinct Smad-binding sites with different binding properties. c-Ski strongly inhibits transactivation of various reporter genes by TGF-beta. c-Ski is incorporated in the Smad DNA binding complex, interferes with the interaction of Smads with a transcriptional co-activator, p300, and in turn recruits HDAC. c-Ski is thus a transcriptional corepressor that links Smads to HDAC in TGF-beta signaling.
引用
收藏
页码:35269 / 35277
页数:9
相关论文
共 71 条
[1]   The CBP co-activator is a histone acetyltransferase [J].
Bannister, AJ ;
Kouzarides, T .
NATURE, 1996, 384 (6610) :641-643
[2]   A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif [J].
Bertolino, E ;
Reimund, B ;
WildtPerinic, D ;
Clerc, RG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (52) :31178-31188
[3]   Transducing the Dpp morphogen gradient in the wing of Drosophila:: Regulation of Dpp targets by brinker [J].
Campbell, G ;
Tomlinson, A .
CELL, 1999, 96 (04) :553-562
[4]   PHOSPHORYLATION-DEPENDENT INTERACTION OF THE CYTOPLASMIC DOMAINS OF THE TYPE-I AND TYPE-II TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS [J].
CHEN, RH ;
MOSES, HL ;
MARUOKA, EM ;
DERYNCK, R ;
KAWABATA, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (20) :12235-12241
[5]   A transcriptional partner for MAD proteins in TGF-beta signalling [J].
Chen, X ;
Rubock, MJ ;
Whitman, M .
NATURE, 1996, 383 (6602) :691-696
[6]   A domain necessary for the transforming activity of SnoN is required for specific DNA binding, transcriptional repression and interaction with TAFII110 [J].
Cohen, SB ;
Nicol, R ;
Stavnezer, E .
ONCOGENE, 1998, 17 (19) :2505-2513
[7]   THE SKI ONCOGENE INDUCES MUSCLE DIFFERENTIATION IN QUAIL EMBRYO CELLS [J].
COLMENARES, C ;
STAVNEZER, E .
CELL, 1989, 59 (02) :293-303
[8]   Transformation of hematopoietic cells by the Ski oncoprotein involves repression of retinoic acid receptor signaling [J].
Dahl, R ;
Kieslinger, M ;
Beug, H ;
Hayman, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (19) :11187-11192
[9]  
Datto MB, 1999, MOL CELL BIOL, V19, P2495
[10]   Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene [J].
Dennler, S ;
Itoh, S ;
Vivien, D ;
ten Dijke, P ;
Huet, S ;
Gauthier, JM .
EMBO JOURNAL, 1998, 17 (11) :3091-3100