Pouponnot C, Jayaraman L, Massagué J
Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Biol Chem. 1998 Sep 4;273(36):22865-8. doi: 10.1074/jbc.273.36.22865.
SMADs are transforming growth factor beta (TGF-beta) receptor substrates and mediators of TGF-beta transcriptional responses. Here we provide evidence that the coactivators p300 and CBP interact with Smads 1 through 4. The biological relevance of this interaction is shown in vivo by overexpression of the adenovirus E1A protein and mutant forms of E1A that lack p300-binding sites. Wild-type E1A, but not the mutants, inhibits SMAD-dependent transcriptional responses to TGF-beta. E1A also inhibits the intrinsic transactivating function of the Smad4 MH2 domain. In addition, overexpression of p300 enhances SMAD-dependent transactivation. Our results suggest a role for p300/CBP in SMAD-mediated transcriptional activation and provide an explanation for the observed ability of E1A to interfere with TGF-beta action.
SMAD 蛋白是转化生长因子β（TGF-β）受体的底物以及 TGF-β转录反应的介质。在此，我们提供证据表明共激活因子 p300 和 CBP 与 Smad1 至 Smad4 相互作用。通过腺病毒 E1A 蛋白及缺乏 p300 结合位点的 E1A 突变体形式的过表达，在体内显示了这种相互作用的生物学相关性。野生型 E1A 而非突变体抑制了对 TGF-β的 SMAD 依赖性转录反应。E1A 还抑制 Smad4 MH2 结构域的内在反式激活功能。此外，p300 的过表达增强了 SMAD 依赖性反式激活。我们的结果表明 p300/CBP 在 SMAD 介导的转录激活中发挥作用，并为观察到的 E1A 干扰 TGF-β作用的能力提供了解释。
