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 journalArticle

Abstract

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
Volume24
Issue number20
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Proteasome Endopeptidase Complex
Microtubules
Suppressor of Cytokine Signaling Proteins
src Homology Domains
Microtubule-Organizing Center
Cytokines
Nocodazole
Ubiquitin
Proteolysis
Proteins
Phosphotransferases
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome. / Vuong, Bao Q.; Arenzana, Teresita L.; Showalter, Brian M.; Losman, Julie; Chen, X. Peter; Mostecki, Justin; Banks, Alexander S.; Limnander, Andre; Fernandez, Neil; Rothman, Paul B.

In: Molecular and Cellular Biology, Vol. 24, No. 20, 10.2004, p. 9092-9101.

Research output: Contribution to journalArticle

Vuong, BQ, Arenzana, TL, Showalter, BM, Losman, J, Chen, XP, Mostecki, J, Banks, AS, Limnander, A, Fernandez, N & Rothman, PB 2004, 'SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome', Molecular and Cellular Biology, vol. 24, no. 20, pp. 9092-9101. https://doi.org/10.1128/MCB.24.20.9092-9101.2004
Vuong, Bao Q. ; Arenzana, Teresita L. ; Showalter, Brian M. ; Losman, Julie ; Chen, X. Peter ; Mostecki, Justin ; Banks, Alexander S. ; Limnander, Andre ; Fernandez, Neil ; Rothman, Paul B. / SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 20. pp. 9092-9101.
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