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

Bao Q. Vuong, Teresita L. Arenzana, Brian M. Showalter, Julie Losman, X. Peter Chen, Justin Mostecki, Alexander S. Banks, Andre Limnander, Neil Fernandez, Paul B. Rothman

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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 2OS 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.

Original languageEnglish (US)
Pages (from-to)9092-9101
Number of pages10
JournalMolecular and cellular biology
Issue number20
StatePublished - Oct 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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