Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region

Somasundaram, Kumaravel ; El-Deiry, Wafik S. (1997) Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region Oncogene, 14 (9). pp. 1047-1057. ISSN 0950-9232

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Official URL: http://www.nature.com/onc/journal/v14/n9/abs/12010...

Abstract

Cellular transformation by the adenovirus E1A oncoprotein requires its p300/CBP- and Rb-binding domains. We mapped inhibition of p53-mediated transactivation to the p300/CBP-binding region of E1A. An E1A mutant incapable of physically interacting with Rb retained the capacity to inhibit transactivation by p53, whereas E1A mutants of the p300/CBP-interacting domain failed to inhibit p53. The inhibitory effect of the p300/CBP-binding region of E1A on p53 was demonstrated with p53-activated reporters and endogenous p53 targets such as p21WAF1/CIP1 or MDM2. E1A lacking the capacity to interact with Rb, but capable of p300/CBP interaction, was competent in suppression of a DNA-damage activated p53-dependent cell cycle checkpoint. Exogenous CBP and p300 were able to individually relieve E1A's inhibitory effect on p53-mediated transcription. Mutants of E1A that are not capable of interacting with p300 or CBP were found to efficiently stabilize endogenous p53 but were not competent in repression of p21 expression thus dissociating these two effects of E1A. Our results suggest that the p300/CBP-binding domain of E1A inhibits a p53-dependent cellular response which normally inhibits DNA replication following Adenovirus infection.

Item Type:Article
Source:Copyright of this article belongs to Nature Publishing Group.
Keywords:E1A; p53; p21WAF1/CIP1; Transformation; Checkpoint; Cancer
ID Code:49719
Deposited On:20 Jul 2011 13:51
Last Modified:20 Jul 2011 13:51

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