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J. Biol. Chem. 281 (13): 8707-8715

© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

p19ras Interacts with and Activates p73 by Involving the MDM2 Protein*{diamondsuit}

Mi-Hee Jeong{ddagger}1, Jeehyeon Bae§1, Won-Ho Kim, Sang-Mi Yoo{ddagger}, Jung-Woong Kim{ddagger}, Peter I. Song||, , and Kyung-Hee Choi{ddagger}2

{ddagger}Laboratory of Molecular Biology, Department of Biological Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Korea, the §Laboratory of Molecular Omics Therapy, Graduate School of Life Science and Biotechnology, Pochon CHA University, Seongnam 463-836, Korea, the Korea Center for Disease Control and Prevention, Korean National Institute of Health, Seoul 122-701, Korea, and the ||Department of Dermatology, University of Colorado Health Sciences Center, Denver, Colorado 80045

Abstract: p73beta is a structural and functional homologue of p53, a tumor suppressor gene. In this study, we identified a novel p73beta-binding protein, p19ras, by the yeast two-hybrid screening method. Alternative splicing of the proto-oncogene H-ras pre-mRNA has led to two distinct transcripts, p19ras and p21ras. In both endogenous and overexpressed systems, we confirmed that p19ras binds to full-length p73beta in vivo and in vitro. Coexpression of p19ras with p73beta stimulated the transcriptional activity of p73beta. Ras proteins are known to be small membrane-localized guanine nucleotide-binding proteins. However, unlike other Ras proteins, p19ras is localized in the nucleus and the cytosol and its interaction with p73beta occurred exclusively in the nucleus. Oncogenic MDM2 (mouse double minutes 2) is a known repressor of p73 transcriptional activity. In this study, when p19ras was bound to MDM2, it further inhibited the association of MDM2 to the p73beta protein. In addition, p19ras abolished MDM2-mediated transcriptional repression of p73beta. Therefore, this study presents a novel pathway of Ras signaling that occurs in the nucleus, involving p19ras and p73beta. Furthermore, a p19ras-mediated novel regulatory mechanism of p73 involving the MDM2 protein is described.


Received for publication December 29, 2005.

* This work was supported by a grant from the Korea Science and Engineering Foundation (R04-2002-000-20112-0). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{diamondsuit} This article was selected as a Paper of the Week.

1 These authors contributed equally to this work.

2 To whom correspondence should be addressed: Laboratory of Molecular Biology, Dept. of Biological Science, College of Natural Sciences, Chung-Ang University, Heuksuk Dong, Dongjak Ku, Seoul 156-756, Korea. Tel.: 82-2-820-5209; Fax: 82-2-824-7302; E-mail: khchoi{at}cau.ac.kr.


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