Zhang H S, Gavin M, Dahiya A, Postigo A A, Ma D, Luo R X, Harbour J W, Dean D C
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cell. 2000 Mar 31;101(1):79-89. doi: 10.1016/S0092-8674(00)80625-X.
We present evidence that Rb forms a repressor containing histone deacetylase (HDAC) and the hSWI/SNF nucleosome remodeling complex, which inhibits transcription of genes for cyclins E and A and arrests cells in the G1 phase of the cell cycle. Phosphorylation of Rb by cyclin D/cdk4 disrupts association with HDAC, relieving repression of the cyclin E gene and G1 arrest. However, the Rb-hSWI/SNF complex persists and is sufficient to maintain repression of the cyclin A and cdc2 genes, inhibiting exit from S phase. HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF then appear to maintain the order of cyclin E and A expression during the cell cycle, which in turn regulates exit from G1 and from S phase, respectively.
我们提供的证据表明,Rb形成一种包含组蛋白脱乙酰基酶(HDAC)和hSWI/SNF核小体重塑复合体的阻遏物,该阻遏物抑制细胞周期蛋白E和A的基因转录,并使细胞停滞在细胞周期的G1期。细胞周期蛋白D/细胞周期蛋白依赖性激酶4(cyclin D/cdk4)对Rb的磷酸化作用破坏了其与HDAC的结合,解除了对细胞周期蛋白E基因的抑制以及G1期停滞。然而,Rb-hSWI/SNF复合体持续存在,并且足以维持对细胞周期蛋白A和细胞分裂周期蛋白2(cdc2)基因的抑制,从而抑制从S期退出。然后,HDAC-Rb-hSWI/SNF和Rb-hSWI/SNF似乎在细胞周期中维持细胞周期蛋白E和A表达的顺序,这反过来又分别调节从G1期和S期退出。