The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation

Jian‐Guo Zhang(Walter and Eliza Hall Institute of Medical Research), Alison Farley(Walter and Eliza Hall Institute of Medical Research), Sandra E. Nicholson(Walter and Eliza Hall Institute of Medical Research), Tracy A. Willson(Walter and Eliza Hall Institute of Medical Research), Lisa M. Zugaro(Walter and Eliza Hall Institute of Medical Research), Richard J. Simpson(Walter and Eliza Hall Institute of Medical Research), Robert L. Moritz(Walter and Eliza Hall Institute of Medical Research), Dale Cary(Walter and Eliza Hall Institute of Medical Research), Rachael T. Richardson(Walter and Eliza Hall Institute of Medical Research), George Hausmann(Walter and Eliza Hall Institute of Medical Research), Benjamin T. Kile(The Royal Melbourne Hospital), Stephen B. H. Kent(Walter and Eliza Hall Institute of Medical Research), Warren S. Alexander(Walter and Eliza Hall Institute of Medical Research), Donald Metcalf(Walter and Eliza Hall Institute of Medical Research), Douglas J. Hilton(Walter and Eliza Hall Institute of Medical Research), Nicos A. Nicola(Walter and Eliza Hall Institute of Medical Research), Manuel Baca(Walter and Eliza Hall Institute of Medical Research)
Proceedings of the National Academy of Sciences
March 2, 1999
10.1073/pnas.96.5.2071
Cited by 632Open Access

Abstract

The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by direct interaction with activated JAKs or with the receptors. These interactions are mediated at least in part by the SH2 domain of SOCS proteins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates interactions with elongins B and C, which in turn may couple SOCS proteins and their substrates to the proteasomal protein degradation pathway. Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway.

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