Are SOCS suppressors, regulators, and degraders

Abstract: Suppressors of cytokine signaling have been identified as inhibitors of cytokine signaling and have been shown to act in a classical feedback loop. The prototype members of this family, cyto-kine-inducible Src homology 2-containing protein and suppressors of cytokine signaling SOC was cloned as cytokine-inducible immediate early gene that could inhibit the activation of signal trans-ducer and activator of transcription factors and block biological responses to several cytokines. Al-though steady progress has been made in the iden-tification of SOCS and their physiological impor-tance, precisely how SOCS proteins function has not yet been discovered. Many recent findings in-dicate that the SOCS act as adaptors that regulate the turnover of certain substrates by interacting with and activating an E3 ubiquitin ligase. Here, I explore recent evidence (presented at the Interna-tional Cytokine Society meeting in Dublin, Ireland, September 2003) that SOCS molecules may not act simply as regulators of cytokine responses but may also play an essential role in determining cell fate and controlling cell differentiation. J. Leukoc