Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A

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(1-3): the retinoblastoma protein (Rb)(4) a transcriptional co-repressor(5), and CBP/p300 (ref. 6), a transcriptional co-activator(7-9). These two proteins locally influence chromatin structure: Rb recruits a histone deacetylase(10-12) whereas CBP is a histone acetyltransferase(13,14). 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(15). 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.