Lai A, Lee J M, Yang W M, DeCaprio J A, Kaelin W G, Seto E, Branton P E
Departments of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Mol Cell Biol. 1999 Oct;19(10):6632-41. doi: 10.1128/MCB.19.10.6632.
Retinoblastoma (RB) tumor suppressor family proteins block cell proliferation in part by repressing certain E2F-specific promoters. Both histone deacetylase (HDAC)-dependent and -independent repression activities are associated with the RB "pocket." The mechanism by which these two repression functions occupy the pocket is unknown. A known RB-binding protein, RBP1, was previously found by our group to be an active corepressor which, if overexpressed, represses E2F-mediated transcription via its association with the pocket. We show here that RBP1 contains two repression domains, one of which binds all three known HDACs and represses them in an HDAC-dependent manner while the other domain functions independently of the HDACs. Thus, RB family members repress transcription by recruiting RBP1 to the pocket. RBP1, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function.
视网膜母细胞瘤（RB）肿瘤抑制家族蛋白部分通过抑制某些E2F特异性启动子来阻断细胞增殖。组蛋白去乙酰化酶（HDAC）依赖性和非依赖性抑制活性均与RB“口袋”相关。这两种抑制功能占据“口袋”的机制尚不清楚。我们小组之前发现一种已知的RB结合蛋白RBP1是一种活性共抑制因子，如果过度表达，它会通过与“口袋”的结合来抑制E2F介导的转录。我们在此表明，RBP1包含两个抑制结构域，其中一个与所有三种已知的HDAC结合，并以HDAC依赖性方式抑制它们，而另一个结构域的功能独立于HDAC。因此，RB家族成员通过将RBP1募集到“口袋”中来抑制转录。反过来，RBP1作为一种桥梁分子来募集HDAC，此外，还提供第二种独立于HDAC的抑制功能。
