SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome.

The regulation of cytokine signaling is critical for controlling cellular proliferation and activation during an immune response. SOCS-1 is a potent inhibitor of Jak kinase activity and of signaling initiated by several cytokines. SOCS-1 protein levels are tightly regulated, and recent data suggest that SOCS-1 may regulate the protein levels ...
of some signaling proteins by the ubiquitin proteasome pathway; however, the cellular mechanism by which SOCS-1 directs proteins for degradation is unknown. In this report, SOCS-1 is found to colocalize and biochemically copurify with the microtubule organizing complex (MTOC) and its associated 20S proteasome. The SOCS-1 SH2 domain is required for the localization of SOCS-1 to the MTOC. Overexpression of SOCS-1 targets Jak1 in an SH2-dependent manner to a perinuclear distribution resembling the MTOC-associated 20S proteasome. Analysis of MTOCs fractionated from SOCS-1-deficient cells demonstrates that SOCS-1 may function redundantly to regulate the localization of Jak1 to the MTOC. Nocodazole inhibits the protein turnover of SOCS-1, demonstrating that the minus-end transport of SOCS-1 to the MTOC-associated 20S proteasome is required to regulate SOCS-1 protein levels. These data link SOCS-1 directly with the proteasome pathway and suggest another function for the SH2 domain of SOCS-1 in the regulation of Jak/STAT signaling.
Mesh Terms:
Animals, Cell Fractionation, Cell Line, Centrosome, Cercopithecus aethiops, Humans, Intracellular Signaling Peptides and Proteins, Janus Kinase 1, Microtubule-Organizing Center, Microtubules, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Recombinant Fusion Proteins, Repressor Proteins, Subcellular Fractions, Suppressor of Cytokine Signaling Proteins
Mol. Cell. Biol.
Date: Oct. 01, 2004
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