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Publication Abstract from PubMed

The ubiquitin-specific protease 8 (USP8)/14-3-3 protein-protein interaction has recently been shown to exert a significant role in the pathogenesis of Cushing's disease (CD). USP8 is a deubiquitinase that prevents epidermal growth factor receptor (EGFR) degradation. Impairment of 14-3-3 binding leads to a higher deubiquitination of EGFR and results in a higher EGFR signaling and an increased production of adrenocorticotropic hormone. Here we report the high-resolution crystal structure of the 14-3-3 binding motif of USP8 surrounding Ser718 in complex with 14-3-3zeta and characterize the interaction with fluorescence polarization and isothermal titration calorimetry. Furthermore, we analyze the effect of USP8 mutations identified in CD on binding to 14-3-3.

Biophysical and structural insight into the USP8/14-3-3 interaction.,Centorrino F, Ballone A, Wolter M, Ottmann C FEBS Lett. 2018 Feb 23. doi: 10.1002/1873-3468.13017. PMID:29473952^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.