p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Binding Sites, Carrier Proteins, Hela Cells, Humans, Immediate-Early Proteins, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Protein Binding, Proteins, Recombinant Proteins, Saccharomyces cerevisiae, Signal Transduction, Ubiquitins, src Homology Domains, src-Family Kinases
J. Biol. Chem.
Date: Aug. 23, 1996
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