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.
Vadlamudi
R K
RK
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Joung
I
I
Strominger
J L
JL
Shin
J
J
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011485:Protein Binding; D011506:Proteins; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D014452:Ubiquitins / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017874:Immediate-Early Proteins; D011506:Proteins; D011994:Recombinant Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014452:Ubiquitins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases