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PMID:11606785

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Citation

Zhang, JG, Metcalf, D, Rakar, S, Asimakis, M, Greenhalgh, CJ, Willson, TA, Starr, R, Nicholson, SE, Carter, W, Alexander, WS, Hilton, DJ and Nicola, NA (2001) The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo. Proc. Natl. Acad. Sci. U.S.A. 98:13261-5

Abstract

Suppressor of Cytokine Signaling-1 (SOCS-1) is an essential physiological inhibitor of IFN-gamma signaling. Mice lacking this gene die in the early postnatal period from a disease characterized by hyperresponsiveness to endogenous IFN-gamma. The SOCS box is a C-terminal domain shared with over 30 other proteins that links SOCS proteins to an E3 ubiquitin ligase activity and the proteasome, but whether it contributes to inhibition of cytokine signaling is currently disputed. We have deleted only the SOCS box of the SOCS-1 gene in mice and show that such mice have an increased responsiveness to IFN-gamma and slowly develop a fatal inflammatory disease. These results demonstrate that deletion of the SOCS box leads to a partial loss of function of SOCS-1.

Links

PubMed PMC60858 Online version:10.1073/pnas.231486498

Keywords

Animals; Carrier Proteins/genetics; Carrier Proteins/physiology; Cells, Cultured; Cytokines/antagonists & inhibitors; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Repressor Proteins; Suppressor of Cytokine Signaling Proteins

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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