Das, Sanjeev and El-Deiry, Wafik S and Somasundaram, Kumaravel (2003) Regulation of the p53 Homolog p73 by Adenoviral Oncogene E1A. In: Journal of Biological Chemistry, 278 (20). pp. 18313-18320.
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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 $p73\alpha$ and $p73\beta$ . 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 $E1A(\Delta 2-36)$. $E1A(\Delta 2-36)$, which does not bind to the p300/CBP family of coactivators, failed to inhibit p73-mediated transcription, whereas $E1A(\Delta CR2)$, 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 $p21^{WAF1/CIP1}$ by E1A. However, p73 was able to induce $p21^{WAF1/CIP1}$ and to mediate growth arrest in the presence of $E1A(\Delta 2-36)$. Furthermore, the expression of either wild-type E1A or $E1A(\Delta 2-36)$ resulted in the stabilization of endogenous p73. However, p73 stabilized in response to the expression of $E1A(\Delta 2-36)$, but not WT E1A, was able to activate the expression of $p21^{WAF1/CIP1}$. 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: | Journal Article |
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Publication: | Journal of Biological Chemistry |
Publisher: | American Society for Biochemistry and Molecular Biology |
Additional Information: | Copyright of this articl ebelongs to American Society for Biochemistry and Molecular Biology. |
Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
Date Deposited: | 12 Oct 2007 |
Last Modified: | 08 Jul 2011 10:52 |
URI: | http://eprints.iisc.ac.in/id/eprint/12248 |
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