STAM-AMSH interaction facilitates the deubiquitination activity in the C-terminal AMSH.
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 approximately 7 microM 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.
Kim
Man Su
MS
Biomedical Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul 136-791, South Korea.
Kim
Jeom-A
JA
Song
Hyun Kyu
HK
Jeon
Hyesung
H
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
D048868:Adaptor Proteins, Signal Transducing; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; C109775:STAM protein, human; C486696:STAMBP protein, human; D025801:Ubiquitin; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase