Phosphorylation of the WWOX Protein Regulates Its Interaction with p73

Noa Lahav, Shahar Rotem-Bamberger, Jamal Fahoum, Emma Joy Dodson, Yahel Kraus, Reem Mousa, Norman Metanis, Assaf Friedler*, Ora Schueler-Furman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


We describe a molecular characterization of the interaction between the cancer-related proteins WWOX and p73. This interaction is mediated by the first of two WW domains (WW1) of WWOX and a PPXY-motif-containing region in p73. While phosphorylation of Tyr33 of WWOX and association with p73 are known to affect apoptotic activity, the quantitative effect of phosphorylation on this specific interaction is determined here for the first time. Using ITC and fluorescence anisotropy, we measured the binding affinity between WWOX domains and a p73 derived peptide, and showed that this interaction is regulated by Tyr phosphorylation of WW1. Chemical synthesis of the phosphorylated domains of WWOX revealed that the binding affinity of WWOX to p73 is decreased when WWOX is phosphorylated. This result suggests a fine-tuning of binding affinity in a differential, ligand-specific manner: the decrease in binding affinity of WWOX to p73 can free both partners to form new interactions.

Original languageAmerican English
Pages (from-to)1843-1851
Number of pages9
Issue number13
StatePublished - 1 Jul 2020

Bibliographical note

Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim


  • WW domains
  • binding affinity
  • context-dependent
  • peptide protein interactions
  • protein phosphorylation
  • regulatory interactions


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