STAM-AMSH interaction facilitates the deubiquitination activity in the C-terminal AMSH

Man S. Kim, Jeom A. Kim, Hyun Kyu Song, Hyesung Jeon

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Signal transducing adaptor molecule (STAM) complexed with hepatocyte growth factor regulated tyrosine kinase substrate (Hrs) works on sorting of cargo proteins in multivesicular body (MVB) pathway. Associated molecule with SH3 domain of STAM (AMSH), a zinc-containing ubiquitin isopeptidase, is thought to play a role in regulation of ubiquitin-mediated degradation by binding to STAM. We have found that AMSH requires the conformation of Px(V/I)(D/N)RxxKP sequence to bind SH3 domain of STAM with ∼7 μM affinity, and that the isolated C-terminal domain of AMSH contains the isopeptidase activity. Deubiquitination by AMSH was assisted when ubiquitins were bound to STAM which can bind to AMSH simultaneously. With the specificity toward K63-linked ubiquitins, this facilitated ubiquitin processing activity of AMSH may imply a distinct regulatory mechanism for sorting and degradation through STAM binding.

Original languageEnglish
Pages (from-to)612-618
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume351
Issue number3
DOIs
Publication statusPublished - 2006 Dec 22

    Fingerprint

Keywords

  • AMSH
  • Deubiquitination
  • Isopeptidase
  • Lysine-63 link
  • Metalloprotease
  • Multivesicular body pathway
  • SH3 domain
  • Signal transduction
  • STAM
  • Ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this