Biophysical and structural insight into the USP8/14‐3‐3 interaction. Issue 7 (2nd March 2018)

• Record Type: Journal Article
• Authors: Centorrino, Federica; Ballone, Alice; Wolter, Madita; Ottmann, Christian
• Is Part Of: FEBS letters. Volume 592:Issue 7(2018)
• Page Start: 1211
• Page End: 1220
• Publication Date: 2018-03-02
• Subjects: 14‐3‐3 proteins -- fluorescence polarization -- isothermal titration calorimetry -- ubiquitin‐specific protease 8 -- X‐ray crystallography; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13017
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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 14‐3‐3ζ 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. Abstract :