Meloni Alison R, Lai Chun-Hsiang, Yao Tso-Pang, Nevins Joseph R
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3054, Durham, North Carolina 27710, USA.
Mol Cancer Res. 2005 Oct;3(10):575-83. doi: 10.1158/1541-7786.MCR-05-0088.
The E2F4 and E2F5 proteins specifically associate with the Rb-related p130 protein in quiescent cells to repress transcription of various genes encoding proteins important for cell growth. A series of reports has provided evidence that Rb-mediated repression involves both histone deacetylase (HDAC)-dependent and HDAC-independent events. Our previous results suggest that one such mechanism for Rb-mediated repression, independent of recruitment of HDAC, involves the recruitment of the COOH-terminal binding protein (CtBP) corepressor, a protein now recognized to play a widespread role in transcriptional repression. We now find that CtBP can interact with the histone acetyltransferase, cyclic AMP--responsive element--binding protein (CREB) binding protein, and inhibit its ability to acetylate histone. This inhibition is dependent on a NH2-terminal region of CtBP that is also required for transcription repression. These results thus suggest two complementary mechanisms for E2F/p130-mediated repression that have in common the control of histone acetylation at target promoters.
在静止细胞中，E2F4和E2F5蛋白特异性地与Rb相关的p130蛋白结合，以抑制各种编码对细胞生长重要的蛋白质的基因的转录。一系列报告提供了证据表明，Rb介导的抑制涉及组蛋白去乙酰化酶（HDAC）依赖性和HDAC非依赖性事件。我们之前的结果表明，Rb介导的抑制的一种这样的机制，独立于HDAC的募集，涉及COOH末端结合蛋白（CtBP）共抑制因子的募集，CtBP现在被认为在转录抑制中起广泛作用。我们现在发现，CtBP可以与组蛋白乙酰转移酶、环磷酸腺苷反应元件结合蛋白（CREB）结合蛋白相互作用，并抑制其乙酰化组蛋白的能力。这种抑制依赖于CtBP的NH2末端区域，该区域也是转录抑制所必需的。因此，这些结果提示了E2F/p130介导的抑制的两种互补机制，它们的共同之处在于控制靶启动子处的组蛋白乙酰化。
