Ait-Si-Ali S, Ramirez S, Barre F X, Dkhissi F, Magnaghi-Jaulin L, Girault J A, Robin P, Knibiehler M, Pritchard L L, Ducommun B, Trouche D, Harel-Bellan A
Laboratoire Oncogénèse, Différenciation et Transduction du Signal, CNRS UPR 9079, Villejuif, France.
Nature. 1998 Nov 12;396(6707):184-6. doi: 10.1038/24190.
Transforming viral proteins such as E1A force cells through the restriction point of the cell cycle into S phase by forming complexes with two cellular proteins: the retinoblastoma protein (Rb), a transcriptional co-repressor, and CBP/p300, a transcriptional co-activator. These two proteins locally influence chromatin structure: Rb recruits a histone deacetylase, whereas CBP is a histone acetyltransferase. Progression through the restriction point is triggered by phosphorylation of Rb, leading to disruption of Rb-associated repressive complexes and allowing the activation of S-phase genes. Here we show that CBP, like Rb, is controlled by phosphorylation at the G1/S boundary, increasing its histone acetyltransferase activity. This enzymatic activation is mimicked by E1A.
诸如E1A之类的转化病毒蛋白通过与两种细胞蛋白形成复合物，迫使细胞穿过细胞周期的限制点进入S期：视网膜母细胞瘤蛋白（Rb），一种转录共抑制因子；以及CBP/p300，一种转录共激活因子。这两种蛋白局部影响染色质结构：Rb招募一种组蛋白脱乙酰酶，而CBP是一种组蛋白乙酰转移酶。穿过限制点是由Rb的磷酸化触发的，导致与Rb相关的抑制复合物的破坏，并允许S期基因的激活。在这里，我们表明，与Rb一样，CBP在G1/S边界受磷酸化控制，增加其组蛋白乙酰转移酶活性。这种酶促激活可被E1A模拟。
