Zhao Ling-Jun, Subramanian T, Vijayalingam S, Chinnadurai G
Institute for Molecular Virology Saint Louis University Health Sciences Center Doisy Research Center 1100 South Grand Blvd St. Louis, Missouri 63104.
Genes Cancer. 2014 Apr;5(1-2):31-40. doi: 10.18632/genesandcancer.2.
C-terminal binding protein (CtBP) family transcriptional corepressors include CtBP1 and CtBP2. While CtBP1 and CtBP2 share significant amino acid sequence homology, CtBP2 possesses a unique N-terminal domain that is modified by acetylation and contributes to exclusive nuclear localization. Although CtBP1 and CtBP2 are functionally redundant for certain activities during vertebrate development, they also perform unique functions. Previous studies have identified several CtBP1-interacting proteins that included other transcriptional corepressors, DNA-binding repressors and histone modifying enzymatic components such as the histone deacetylases and the histone demethylase LSD-1. Here, we carried out an unbiased proteomic analysis of CtBP2-associated proteins and discovered the association of several components of the CtBP1 proteome as well as novel interactions. The CtBP2 proteome contained components of the NuRD complex and the E2F family member E2F7. E2F7 interacted with the hydrophobic cleft region of CtBP1 and CtBP2 through a prototypical CtBP binding motif, PIDLS. E2F7 repressed E2F1 transcription, inhibited cell proliferation in a CtBP-dependent fashion. Our study identified CtBP as a corepressor of E2F7 and as a regulator of DNA damage response.
C末端结合蛋白（CtBP）家族转录共抑制因子包括CtBP1和CtBP2。虽然CtBP1和CtBP2具有显著的氨基酸序列同源性，但CtBP2拥有一个独特的N末端结构域，该结构域通过乙酰化修饰，有助于其特有的核定位。尽管在脊椎动物发育过程中，CtBP1和CtBP2在某些活动中功能冗余，但它们也执行独特的功能。先前的研究已经鉴定出几种与CtBP1相互作用的蛋白质，包括其他转录共抑制因子、DNA结合抑制因子以及组蛋白修饰酶成分，如组蛋白去乙酰化酶和组蛋白去甲基化酶LSD-1。在这里，我们对与CtBP2相关的蛋白质进行了无偏倚的蛋白质组学分析，发现了CtBP1蛋白质组的几个成分以及新的相互作用。CtBP2蛋白质组包含NuRD复合物的成分和E2F家族成员E2F7。E2F7通过典型的CtBP结合基序PIDLS与CtBP1和CtBP2的疏水裂隙区域相互作用。E2F7抑制E2F1转录，以CtBP依赖的方式抑制细胞增殖。我们的研究确定CtBP是E2F7的共抑制因子和DNA损伤反应的调节因子。
