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

Mol Cell Biol. 2004 Oct;24(20):9092-101. doi: 10.1128/MCB.24.20.9092-9101.2004.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Fractionation
  • Cell Line
  • Centrosome / chemistry
  • Centrosome / metabolism
  • Chlorocebus aethiops
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Janus Kinase 1
  • Microtubule-Organizing Center / metabolism*
  • Microtubules / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Subcellular Fractions / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins


  • Intracellular Signaling Peptides and Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Janus Kinase 1
  • Proteasome Endopeptidase Complex