The three members of the pocket proteins family share the ability to regress E2F activity through recruitment of a histone deacetylase
The three members of the pocket proteins family share the ability to regress E2F activity through recruitment of a histone deacetylase
复制标题
DOI：
10.1073/pnas.95.18.10493
复制
发表时间：
1998-09-01
影响因子：
11.1
通讯作者：
Trouche, D
中科院分区：
文献类型：
--
作者：
Ferreira, R;Magnaghi-Jaulin, L;Trouche, D
转录因子E2F在哺乳动物细胞的细胞周期调控中起着重要作用。E2F结合位点存在于S阶段所需的多种基因的启动子中，在承诺点从负转录转变为正转录，这是G(1)/S转变之前GR中的一个关键点。在承诺点之前，E2F活性受到口袋蛋白家族成员的抑制。这种抑制被认为是适当控制细胞生长的关键。我们以前已经证明了Pocket蛋白家族的创始成员Rb通过招募组蛋白去乙酰基酶HDAC1来抑制E2F1的活性，在这里，我们发现Pocket蛋白家族的另外两个成员p107和p130也能够在活细胞中与HDAC1物理相互作用，KDAC1通过一个类似于病毒转化蛋白结合和失活Pocket蛋白的“LXCXE”基序与p107和Rb相互作用。事实上，我们发现病毒转化蛋白E1a与HDAC1竞争p107相互作用。我们还证明了p107能够同时与HDAC1和E2F4相互作用，提出了一种p107招募HDAC1来抑制E2F位点的模型。事实上，我们证明了组蛋白脱乙酰酶活性参与了p107或p130诱导的E2F4的抑制，综上所述，我们的数据表明，E2F家族的所有成员在G(1)早期都受到类似的复合体的调节，包含一个口袋蛋白和组蛋白脱乙酰基酶HDAC1。
The transcription factor E2F plays a major role in cell cycle control in mammalian cells. E2F binding sites, which are present in the promoters of a variety of genes required for S phase, shift from a negative to a positive role in transcription at the commitment point, a crucial point in Gr that precedes the G(1)/S transition. Before the commitment point, E2F activity is repressed by members of the pocket proteins family. This repression is believed to be crucial for the proper control of cell growth. We have previously shown that Rb, the founding member of the pocket proteins family, represses E2F1 activity by recruiting the histone deacetylase HDAC1, Here, we show that the two other members of the pocket proteins family, p107 and p130, also are able to interact physically with HDAC1 in live cells, KDAC1 interacts with p107 and Rb through an "LXCXE"-like motif, similar to that used by viral transforming proteins to bind and inactivate pocket proteins. Indeed, we find that the viral transforming protein E1A competes with HDAC1 for p107 interaction. We also demonstrate that p107 is able to interact simultaneously with HDAC1 and E2F4, suggesting a model in which p107 recruits HDAC1 to repress E2F sites. Indeed, we demonstrate that histone deacetylase activity is involved in the p107- or p130-induced repression of E2F4, Taken together, our data suggest that all members of the E2F family are regulated in early G(1) by similar complexes, containing a pocket protein and the histone deacetylase HDAC1.