Biophysical and structural insight into the USP8/14-3-3 interaction

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

4 Citaten (Scopus)
54 Downloads (Pure)


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.

Originele taal-2Engels
Pagina's (van-tot)1211-1220
Aantal pagina's10
TijdschriftFEBS Letters
Nummer van het tijdschrift7
StatusGepubliceerd - apr 2018


Citeer dit