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Phosphorylation of the WWOX Protein Regulates Its Interaction with p73
Author(s) -
Lahav Noa,
RotemBamberger Shahar,
Fahoum Jamal,
Dodson EmmaJoy,
Kraus Yahel,
Mousa Reem,
Metanis Norman,
Friedler Assaf,
SchuelerFurman Ora
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000032
Subject(s) - wwox , phosphorylation , fluorescence anisotropy , chemistry , peptide , cancer research , microbiology and biotechnology , biophysics , biochemistry , biology , gene , suppressor , membrane
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.