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Tumor suppressor WWOX binds to ΔNp63α and sensitizes cancer cells to chemotherapy

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journal contribution
posted on 19.11.2013, 14:30 by Z. Salah, T. Bar-mag, Y. Kohn, F. Pichiorri, T. Palumbo, Gerry Melino, R.A. Aqeilan
The WWOX tumor suppressor is a WW domain-containing protein. Its function in the cell has been shown to be mediated, in part, by interacting with its partners through its first WW (WW1) domain. Here, we demonstrated that WWOX via WW1 domain interacts with p53 homolog, ΔNp63α. This protein–protein interaction stabilizes ΔNp63α, through antagonizing function of the E3 ubiquitin ligase ITCH, inhibits nuclear translocation of ΔNp63α into the nucleus and suppresses ΔNp63α transactivation function. Additionally, we found that this functional crosstalk reverses cancer cells resistance to cisplatin, mediated by ΔNp63α, and consequently renders these cells more sensitive to undergo apoptosis. These findings suggest a functional crosstalk between WWOX and ΔNp63α in tumorigenesis.

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Citation

Cell Death and Disease, 2013, 4, e480

Version

VoR (Version of Record)

Published in

Cell Death and Disease

Publisher

Nature Publishing Group for Associazione Differenziamento e Morte Cellulare

eissn

2041-4889

Available date

19/11/2013

Publisher version

http://www.nature.com/cddis/journal/v4/n1/full/cddis20136a.html

Language

en

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