Functional association between Wwox tumor suppressor protein and p73, a p53 homolog
- 30 March 2004
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (13) , 4401-4406
- https://doi.org/10.1073/pnas.0400805101
Abstract
The WWOX gene is a recently cloned tumor suppressor gene that spans the FRA16D fragile region. Wwox protein contains two WW domains that are generally known to mediate protein–protein interaction. Here we show that Wwox physically interacts via its first WW domain with the p53 homolog, p73. The tyrosine kinase, Src, phosphorylates Wwox at tyrosine 33 in the first WW domain and enhances its binding to p73. Our results further demonstrate that Wwox expression triggers redistribution of nuclear p73 to the cytoplasm and, hence, suppresses its transcriptional activity. In addition, we show that cytoplasmic p73 contributes to the proapoptotic activity of Wwox. Our findings reveal a functional cross-talk between p73 and Wwox tumor suppressor protein.Keywords
This publication has 25 references indexed in Scilit:
- JNK1 Physically Interacts with WW Domain-containing Oxidoreductase (WOX1) and Inhibits WOX1-mediated ApoptosisJournal of Biological Chemistry, 2003
- Mechanism of action of interleukin-2 (IL-2)-Bax, an apoptosis-inducing chimaeric protein targeted against cells expressing the IL-2 receptorBiochemical Journal, 2003
- Nuclear Import and Export Signals in Control of the p53-related Protein p73Journal of Biological Chemistry, 2002
- Physical Interaction of p73 with c-Myc and MM1, a c-Myc-binding Protein, and Modulation of the p73 FunctionPublished by Elsevier ,2002
- Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumorsOncogene, 2002
- Human ΔNp73 regulates a dominant negative feedback loop for TAp73 and p53Cell Death & Differentiation, 2001
- FRA3B and other common fragile sites: the weakest linksNature Reviews Cancer, 2001
- Hyaluronidase Induction of a WW Domain-containing Oxidoreductase That Enhances Tumor Necrosis Factor CytotoxicityJournal of Biological Chemistry, 2001
- Physical Interaction with Yes-associated Protein Enhances p73 Transcriptional ActivityJournal of Biological Chemistry, 2001
- Catalytic specificity of protein-tyrosine kinases is critical for selective signallingNature, 1995