p62, a phosphotyrosine-independent ligand of the SH2 domain of p56(lck), belongs to a new class of ubiquitin-binding proteins

Ratna K. Vadlamudi, Insil Joung, Jack L. Strominger, Jaekyoon Shin

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Abstract

p62 is a novel cellular protein which was initially identified as a phosphotyrosine-independent ligand of the SH2 domain of p56(lck). In the yeast two-hybrid system, p62 specifically interacted with ubiquitin in vivo. Furthermore, p62 bound to ubiquitin-conjugated Sepharose beads in vitro and was efficiently competed by soluble ubiquitin. The interaction was independent of ATP hydrolysis, and its dissociation did not require a reducing agent. Thus, p62 binds to ubiquitin noncovalently. Further analysis showed that the C-terminal 80 amino acids of p62 were indispensable for its interaction with ubiquitin. However, p62 has homology neither with ubiquitin C-terminal hydrolases nor with the S5a subunit of the 26 S proteasome complex, the only proteins known to bind to ubiquitin noncovalently. These results suggest that p62 belongs to a new class of ubiquitin-binding proteins and that p62 affects signal transduction at least partly through ubiquitination-mediated protein degradation.

Original languageEnglish (US)
Pages (from-to)20235-20237
Number of pages3
JournalJournal of Biological Chemistry
Volume271
Issue number34
DOIs
StatePublished - Sep 5 1996

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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