Binding of pRB to the PHD protein RBP2 promotes cellular differentiation
Binding of pRB to the PHD protein RBP2 promotes cellular differentiation
复制标题
DOI：
10.1016/j.molcel.2005.05.012
复制
发表时间：
2005-06-10
期刊：
影响因子：
16
通讯作者：
Kaelin, WG
中科院分区：
文献类型：
--
作者：
Benevolenskaya, EV;Murray, HL;Kaelin, WG
pRB可以通过抑制e2f响应启动子来加强G1阻断。它还能协同激活某些非e2f转录因子并促进分化。一些pRB变体激活转录并促进分化，尽管E2F结合和转录抑制能力受损。我们在筛选与这些pRB变体结合的蛋白质时发现了RBP2。RBP2类似于其他染色质相关的转录调节因子，RBP2结合与pRB激活转录和促进分化的能力有关。在分化细胞分离的染色质中检测到RBP2和pRB共定位和pRB/RBP2复合物。在共激活和分化实验中，RBP2 siRNA表型显示pRB功能的恢复，表明pRB阻止RBP2抑制分化所需的基因。此外，两个含溴结构域的蛋白被鉴定为RBP2靶点，它们以RBP2依赖的方式被pRB转录激活。我们的研究结果表明，pRB促进分化涉及游离RBP2的中和和与常染色质维持相关的RBP2靶点的转录激活。
pRB can enforce a G1 block by repressing E2F-responsive promoters. It also coactivates certain non-E2F transcription factors and promotes differentiation. Some pRB variants activate transcription and promote differentiation despite impaired E2F binding and transcriptional repression capabilities. We identified RBP2 in a screen for proteins that bind to such pRB variants. RBP2 resembles other chromatin-associated transcriptional regulators and RBP2 binding tracked with pRB's ability to activate transcription and promote differentiation. RBP2 and pRB colocalize and pRB/RBP2 complexes were detected in chromatin isolated from differentiating cells. RBP2 siRNA phenocopied restoration of pRB function in coactivation and differentiation assays, suggesting that pRB prevents RBP2 from repressing genes required for differentiation. In addition, two bromodomain-containing proteins were identified as RBP2 targets that are transcriptionally activated by pRB in an RBP2-dependent manner. Our results suggest that promotion of differentiation by pRB involves neutralization of free RBP2 and transcriptional activation of RBP2 targets linked to euchromatin maintenance.