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

Korea University, Sŏul, Seoul, South Korea
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 01/2007; 351(3):612-8. DOI: 10.1016/j.bbrc.2006.10.068
Source: PubMed


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.

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Available from: Hyun Kyu Song, Dec 26, 2013
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    • "Results from numerous studies in cultured cells have shown that the Hrs/Stam complex is required for attenuation of Epidermal Growth Factor Receptor (EFGR) signaling and suggested a general function in RTK down regulation. However, the Stam protein was reported to interact with deubiquitination enzymes [15], [16], raising the possibility that it can also contribute, in interaction with or independently of Hrs, to disengagement of the cargo from the degradation pathway. Therefore, the full deciphering of the role of Hrs and Stam requires in vivo analysis of their respective function during the different processes that are regulated by signalling pathways during development. "
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