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

Research output: Contribution to journalArticle

178 Citations (Scopus)

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 languageEnglish
Pages (from-to)4401-4406
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number13
DOIs
Publication statusPublished - Mar 30 2004

Fingerprint

Proteins
src-Family Kinases
Tumor Suppressor Genes
Tyrosine
Cytoplasm
Genes
Tumor Protein p73

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Aqeilan, R. I., Pekarsky, Y., Herrero, J. J., Palamarchuk, A., Letofsky, J., Druck, T., ... 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

Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. / Aqeilan, Rami I.; Pekarsky, Yuri; Herrero, Juan J.; Palamarchuk, Alexey; Letofsky, Jean; Druck, Teresa; Trapasso, Francesco; Han, Shuang Yin; Melino, Gerry; Huebner, Kay; Croce, Carlo M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 13, 30.03.2004, p. 4401-4406.

Research output: Contribution to journalArticle

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
Aqeilan, Rami I. ; Pekarsky, Yuri ; Herrero, Juan J. ; Palamarchuk, Alexey ; Letofsky, Jean ; Druck, Teresa ; Trapasso, Francesco ; Han, Shuang Yin ; Melino, Gerry ; Huebner, Kay ; Croce, Carlo M. / Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 13. pp. 4401-4406.
@article{c9313bc1c1d74daca3bb42b4dae120fb,
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.}",
year = "2004",
month = "3",
day = "30",
doi = "10.1073/pnas.0400805101",
language = "English",
volume = "101",
pages = "4401--4406",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=12144289659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12144289659&partnerID=8YFLogxK

U2 - 10.1073/pnas.0400805101

DO - 10.1073/pnas.0400805101

M3 - Article

C2 - 15070730

AN - SCOPUS:12144289659

VL - 101

SP - 4401

EP - 4406

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -