Functional association between Wwox tumor suppressor protein and p73, a p53 homolog

Rami I. Aqeilan, Yuri Pekarsky, Juan J. Herrero, Alexey Palamarchuk, Jean Letofsky, Teresa Druck, Francesco Trapasso, Shuang Yin Han, Gerry Melino, Kay Huebner, Carlo M. Croce*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

204 Scopus citations


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.

Original languageAmerican English
Pages (from-to)4401-4406
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - 30 Mar 2004
Externally publishedYes


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