Adenoviral E1A targets Mdm4 to stabilize tumor suppressor

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/4619

Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/4619

Title:	Adenoviral E1A targets Mdm4 to stabilize tumor suppressor
Authors:	Li, Z.;Day, C-P.;Yang, J-Y.;Tsai, W-B.;Lozano, G.;Shih, H-M.;Mien-Chie Hung
Date:	2004-12
Issue Date:	2009-11-27 05:57:05 (UTC+0)
Publisher:	Asia University
Abstract:	The adenoviral protein E1A associates with multiple anticancer activities, including stabilization of p53 tumor suppressor, and has been tested through gene therapy approaches in clinical trials. To identify potential E1A-binding proteins involved in E1A?s anticancer activities, we screened a yeast two-hybrid library and identified Mdm4, an Mdm2-related p53-binding protein, as a novel E1A-binding protein. The NH2-terminal region of Mdm4 and the CR1 domain of E1A were required for the interaction between E1A and Mdm4. E1A preferentially bound to Mdm4 rather than Mdm2 and formed a complex with p53 in the presence of Mdm4, resulting in the stabilization of p53 in a p14ARF-independent manner. E1A failed to stabilize p53 in the absence of Mdm4, showing that Mdm4 was required for p53 stabilization by E1A. Moreover, E1A-mediated stabilization of p53 occurred in nucleus. Although it had no effect on the p53-Mdm2 interaction, E1A facilitated Mdm4 binding to p53 and inhibited Mdm2 binding to Mdm4, resulting in decreased nuclear exportation of p53. Thus, our findings highlighted a novel mechanism, whereby E1A stabilized the p53 tumor suppressor through Mdm4.
Relation:	CANCER RESEARCH 64:9080-9085
Appears in Collections:	[生物科技學系] 期刊論文

Files in This Item:

File	Description	Size	Format
		0Kb	Unknown	658	View/Open
310904400-4619 .doc		30Kb	Microsoft Word	779	View/Open