进化上保守的多亚基RBL2/p130和E2F4蛋白复合物在静止期抑制人类细胞周期依赖性基因。

Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.

作者信息

Litovchick Larisa, Sadasivam Subhashini, Florens Laurence, Zhu Xiaopeng, Swanson Selene K, Velmurugan Soundarapandian, Chen Runsheng, Washburn Michael P, Liu X Shirley, DeCaprio James A

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

出版信息

Mol Cell. 2007 May 25;26(4):539-51. doi: 10.1016/j.molcel.2007.04.015.

DOI:10.1016/j.molcel.2007.04.015

PMID:17531812

Abstract

The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence.

摘要

包括pRB、p107和p130在内的哺乳动物视网膜母细胞瘤（RB）家族通过尚未完全了解的机制抑制E2F靶基因。在黑腹果蝇中，RB依赖性抑制部分由多亚基蛋白复合物果蝇RBF、E2F和Myb（dREAM）介导，该复合物包含秀丽隐杆线虫合成多外阴B类（synMuvB）基因产物的同源物。通过结合蛋白质组学、基因组学和生物信息学分析的综合方法，我们鉴定出一种称为DP、RB样、E2F和MuvB（DREAM）的p130复合物，它包含synMuvB蛋白LIN-9、LIN-37、LIN-52、LIN-54和LIN-53/RBBP4的哺乳动物同源物。DREAM在G0期与800多个人类启动子结合，是抑制E2F靶基因所必需的。在S期，MuvB蛋白从p130上解离，形成一个与MYB结合的独特子模块。这项工作揭示了一种进化上保守的多亚基蛋白复合物，它包含p130和E2F4，但不包含pRB，并在静止期介导细胞周期依赖性基因的抑制。