HISTONE ACETYLTRANSFERASE ACTIVITY OF CBP IS CONTROLLED BY CYCLE-DEPENDENT KINASES AND ONCOPROTEIN E1A

Transforming viral proteins such as E1A force cells through the restri ction point of the cell cycle into S phase by forming complexes with t wo cellular proteins(1-3): the retinoblastoma protein (Rb)(4) a transc riptional co-repressor(5), and CBP/p300 (ref. 6), a transcriptional co -activator(7-9). These two proteins locally influence chromatin struct ure: Rb recruits a histone deacetylase(10-12) whereas CBP is a histone acetyltransferase(13,14). Progression through the restriction point i s triggered by phosphorylation of Rb, leading to disruption of Rb-asso ciated repressive complexes and allowing the activation of S-phase gen es(15). Here we show that CBP, like Rb, is controlled by phosphorylati on at the G1/S boundary, increasing its histone acetyltransferase acti vity. This enzymatic activation is mimicked by E1A.