Strober B E, Dunaief J L, Goff S P
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Mol Cell Biol. 1996 Apr;16(4):1576-83. doi: 10.1128/MCB.16.4.1576.
hBRG1 and hBRM are mammalian homologs of the SNF2/SW12 yeast transcriptional activator. These proteins exist in a large multisubunit complex that likely serves to remodel chromatin and, in so doing, facilitates the function of specific transcription factors. The retinoblastoma protein (pRB) inhibits cell cycle progression by repressing transcription of specific growth-related genes. Using the yeast two-hybrid system, we demonstrate that the members of the hBRG1/hBRM family of proteins interact with the pRB family of proteins, which includes pRB, p107, and p130. Interaction between the hBRG1/hBRM family with the pRB family likely influences cellular proliferation, as both hBRG1 and hBRM, but not mutants of these proteins unable to bind to pRB family members, inhibit the formation of drug-resistant colonies when transfected into the SW13 human adenocarcinoma cell line, which lacks endogenous hBRG1 or hBRM. Further, hBRM and two isoforms of hBRG1 induce the formation of flat, growth-arrested cells in a pRB family-dependent manner when introduced into SW13 cells. This flat-cell inducing activity is severely reduced by cotransfection of the wild-type E1A protein and variably reduced by the cotransfection of mutants of E1A that lack the ability to bind to some or all members of the pRB family.
hBRG1和hBRM是酵母转录激活因子SNF2/SW12的哺乳动物同源物。这些蛋白质存在于一个大型多亚基复合物中，该复合物可能用于重塑染色质，并以此促进特定转录因子的功能。视网膜母细胞瘤蛋白（pRB）通过抑制特定生长相关基因的转录来抑制细胞周期进程。利用酵母双杂交系统，我们证明hBRG1/hBRM蛋白家族的成员与pRB蛋白家族相互作用，pRB蛋白家族包括pRB、p107和p130。hBRG1/hBRM家族与pRB家族之间的相互作用可能影响细胞增殖，因为当hBRG1和hBRM转染到缺乏内源性hBRG1或hBRM的SW13人腺癌细胞系中时，它们能抑制耐药菌落的形成，但这些蛋白中不能与pRB家族成员结合的突变体则无此作用。此外，当将hBRM和hBRG1的两种异构体导入SW13细胞时，它们以pRB家族依赖的方式诱导扁平的、生长停滞的细胞形成。野生型E1A蛋白共转染会严重降低这种扁平细胞诱导活性，而缺乏与pRB家族部分或所有成员结合能力的E1A突变体共转染则会使其活性不同程度降低。
