TY - JOUR
T1 - Phosphorylation of the WWOX Protein Regulates Its Interaction with p73
AU - Lahav, Noa
AU - Rotem-Bamberger, Shahar
AU - Fahoum, Jamal
AU - Dodson, Emma Joy
AU - Kraus, Yahel
AU - Mousa, Reem
AU - Metanis, Norman
AU - Friedler, Assaf
AU - Schueler-Furman, Ora
N1 - Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - WW domains
KW - binding affinity
KW - context-dependent
KW - peptide protein interactions
KW - protein phosphorylation
KW - regulatory interactions
UR - http://www.scopus.com/inward/record.url?scp=85083460865&partnerID=8YFLogxK
U2 - 10.1002/cbic.202000032
DO - 10.1002/cbic.202000032
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C2 - 32185845
AN - SCOPUS:85083460865
SN - 1439-4227
VL - 21
SP - 1843
EP - 1851
JO - ChemBioChem
JF - ChemBioChem
IS - 13
ER -
