Phosphorylation of the WWOX Protein Regulates Its Interaction with p73 |
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| Authors: | Dr Noa Lahav Dr Shahar Rotem-Bamberger Jamal Fahoum Emma-Joy Dodson Yahel Kraus Reem Mousa Dr Norman Metanis Dr Assaf Friedler Dr Ora Schueler-Furman |
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| Affiliation: | 1. The Institute of Chemistry, The Hebrew University of Jerusalem Edmond J. Safra Campus, Givat Ram, 91904 Jerusalem, Israel;2. Department of Microbiology and Molecular Genetics, Institute of Biomedical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Hadassah Medical School POB 12272, 91120 Jerusalem, Israel |
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| Abstract: | 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. |
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| Keywords: | context-dependent regulatory interactions peptide protein interactions protein phosphorylation binding affinity WW domains |
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