Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

The Many Faces of MDM2 Binding Partners.
M. F. Riley and G. Lozano (2012)
Genes & Cancer 3, 226-239
   Abstract »    Full Text »    PDF »
H-Ras Localizes to Cell Nuclei and Varies with the Cell Cycle.
S. Contente, T.-J. A. Yeh, and R. M. Friedman (2011)
Genes & Cancer 2, 166-172
   Abstract »    Full Text »    PDF »
Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged.
C. J. David and J. L. Manley (2010)
Genes & Dev. 24, 2343-2364
   Abstract »    Full Text »    PDF »
Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis.
M. Tozluoglu, E. Karaca, T. Haliloglu, and R. Nussinov (2008)
Nucleic Acids Res. 36, 5033-5049
   Abstract »    Full Text »    PDF »
TIP60 Represses Transcriptional Activity of p73{beta} via an MDM2-bridged Ternary Complex.
J.-W. Kim, P. I. Song, M.-H. Jeong, J.-H. An, S.-Y. Lee, S.-M. Jang, K.-H. Song, C. A. Armstrong, and K.-H. Choi (2008)
J. Biol. Chem. 283, 20077-20086
   Abstract »    Full Text »    PDF »
Role of Activating Transcription Factor 3 on TAp73 Stability and Apoptosis in Paclitaxel-Treated Cervical Cancer Cells.
Y. K. Oh, H. J. Lee, M.-H. Jeong, M. Rhee, J.-W. Mo, E. H. Song, J.-Y. Lim, K.-H. Choi, I. Jo, S. I. Park, et al. (2008)
Mol. Cancer Res. 6, 1232-1249
   Abstract »    Full Text »    PDF »
Regulation of H-ras Splice Variant Expression by Cross Talk between the p53 and Nonsense-Mediated mRNA Decay Pathways.
J. Barbier, M. Dutertre, D. Bittencourt, G. Sanchez, L. Gratadou, P. de la Grange, and D. Auboeuf (2007)
Mol. Cell. Biol. 27, 7315-7333
   Abstract »    Full Text »    PDF »
p19ras Brings a New Twist to the Regulation of p73 by Mdm2.
K. L. Harms and X. Chen (2006)
Sci. STKE 2006, pe24
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882