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

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
50 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1211-1220
Number of pages10
JournalFEBS Letters
Volume592
Issue number7
DOIs
Publication statusPublished - Apr 2018

    Fingerprint

Keywords

  • 14-3-3 proteins
  • Fluorescence polarization
  • Isothermal titration calorimetry
  • Ubiquitin-specific protease 8
  • X-ray crystallography
  • isothermal titration calorimetry
  • fluorescence polarization
  • ubiquitin-specific protease 8
  • Endopeptidases/chemistry
  • Humans
  • Pituitary ACTH Hypersecretion/genetics
  • Crystallography, X-Ray
  • Ubiquitin Thiolesterase/chemistry
  • ErbB Receptors/genetics
  • Proteolysis
  • Protein Structure, Quaternary
  • 14-3-3 Proteins/chemistry
  • Endosomal Sorting Complexes Required for Transport/chemistry

Cite this