Regulation of the p53 homolog p73 by adenoviral oncogene E1A

Das, Sanjeev ; El-Deiry, Wafik S. ; Somasundaram, Kumaravel (2003) Regulation of the p53 homolog p73 by adenoviral oncogene E1A Journal of Biological Chemistry, 278 (20). pp. 18313-18320. ISSN 0021-9258

Full text not available from this repository.

Official URL: http://www.jbc.org/content/278/20/18313.short

Related URL: http://dx.doi.org/10.1074/jbc.M211704200

Abstract

p73 is a p53 homolog, as they are similar structurally and functionally. Unlike p53, p73 is not inactivated by the products of viral oncogenes such as SV40 T antigen and human papilloma virus E6. Here we show that the product of adenoviral oncogene E1A inhibits the transcriptional activation by both p73α and p73β. Electrophoretic mobility shift assays revealed that E1A does not inhibit the sequence-specific DNA binding by p73. Transcriptional activation by a fusion protein containing the Gal4 DNA-binding domain and either of the activation domains of p73 was inhibited by wild-type (WT) E1A, but not by the N-terminal deletion mutant E1A(Δ2-36). E1A(Δ2-36), which does not bind to the p300/CBP family of coactivators, failed to inhibit p73-mediated transcription, whereas E1A(ΔCR2), a deletion mutant that does not bind to the pRb family of proteins, inhibited p73-mediated transcription as efficiently as WT E1A. Consistent with these observations, growth arrest induced by p73 expressed from a recombinant adenovirus was abrogated by WT E1A, which correlated with inhibition of p73-mediated induction of p21WAF1/CIP1 by E1A. However, p73 was able to induce p21WAF1/CIP1 and to mediate growth arrest in the presence of E1A(Δ2-36). Furthermore, the expression of either wild-type E1A or E1A(Δ2-36) resulted in the stabilization of endogenous p73. However, p73 stabilized in response to the expression of E1A(Δ2-36), but not WT E1A, was able to activate the expression of p21WAF1/CIP1. These results suggest that the transcriptional activation function of p73 is specifically targeted by E1A through a mechanism involving p300/CBP proteins during the process of transformation and that p73 may have a role to play as a tumor suppressor.

Item Type:Article
Source:Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
ID Code:49706
Deposited On:20 Jul 2011 13:53
Last Modified:20 Jul 2011 13:53

Repository Staff Only: item control page