Akiyoshi S, Inoue H, Hanai J, Kusanagi K, Nemoto N, Miyazono K, Kawabata M
Department of Biochemistry, The Cancer Institute of Japanese Foundation for Cancer Research, Research for the Future Program, Japan Society for Promotion of Science, 1-37-1, Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
J Biol Chem. 1999 Dec 3;274(49):35269-77. doi: 10.1074/jbc.274.49.35269.
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 Smad3 with a transcriptional co-activator, p300, and in turn recruits HDAC. c-Ski is thus a transcriptional co-repressor that links Smads to HDAC in TGF-beta signaling.
Smads是转化生长因子-β（TGF-β）超家族的细胞内信号转导介质，可调节多种生物学过程。其中，Smads 2和3被TGF-β特异性激活。我们鉴定出c-Ski是一种与Smad2相互作用的蛋白。c-Ski是v-ski癌基因产物的细胞同源物，已证明它通过募集组蛋白脱乙酰基酶（HDAC）来抑制转录。Smad2/3以TGF-β依赖的方式通过其C末端MH2结构域与c-Ski相互作用。c-Ski包含两个具有不同结合特性的不同Smad结合位点。c-Ski强烈抑制TGF-β对各种报告基因的反式激活。c-Ski被纳入Smad DNA结合复合物中，干扰Smad3与转录共激活因子p300的相互作用，进而募集HDAC。因此，c-Ski是一种转录共抑制因子，在TGF-β信号传导中将Smads与HDAC联系起来。
