| First Author | Vuong BQ | Year | 2004 |
| Journal | Mol Cell Biol | Volume | 24 |
| Issue | 20 | Pages | 9092-101 |
| PubMed ID | 15456882 | Mgi Jnum | J:93318 |
| Mgi Id | MGI:3056850 | Doi | 10.1128/MCB.24.20.9092-9101.2004 |
| Citation | Vuong BQ, et al. (2004) SOCS-1 Localizes to the Microtubule Organizing Complex-Associated 20S Proteasome. Mol Cell Biol 24(20):9092-101 |
| abstractText | 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. |
