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

doi:10.1073/pnas.0400805101

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 journal › Article › peer-review

205 Scopus citations

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.

Original language	English
Pages (from-to)	4401-4406
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	13
DOIs	https://doi.org/10.1073/pnas.0400805101
State	Published - 30 Mar 2004
Externally published	Yes

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Aqeilan, R. I., Pekarsky, Y., Herrero, J. J., Palamarchuk, A., Letofsky, J., Druck, T., Trapasso, F., Han, S. Y., Melino, G., Huebner, K., & Croce, C. M. (2004). Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proceedings of the National Academy of Sciences of the United States of America, 101(13), 4401-4406. https://doi.org/10.1073/pnas.0400805101

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

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.",

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

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Aqeilan, RI, Pekarsky, Y, Herrero, JJ, Palamarchuk, A, Letofsky, J, Druck, T, Trapasso, F, Han, SY, Melino, G, Huebner, K & Croce, CM 2004, 'Functional association between Wwox tumor suppressor protein and p73, a p53 homolog', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 13, pp. 4401-4406. https://doi.org/10.1073/pnas.0400805101

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T1 - Functional association between Wwox tumor suppressor protein and p73, a p53 homolog

AU - Aqeilan, Rami I.

AU - Pekarsky, Yuri

AU - Herrero, Juan J.

AU - Palamarchuk, Alexey

AU - Letofsky, Jean

AU - Druck, Teresa

AU - Trapasso, Francesco

AU - Han, Shuang Yin

AU - Melino, Gerry

AU - Huebner, Kay

AU - Croce, Carlo M.

PY - 2004/3/30

Y1 - 2004/3/30

N2 - 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.

AB - 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.

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

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