Are SOCS suppressors, regulators, and degraders?

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, cytokine-inducible Sire 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 transducer and activator of transcription factors and block biological responses to several cytokines. Although steady progress has been made in the identification of SOCS and their physiological importance, precisely how SOCS proteins function has not yet been discovered. Many recent findings indicate 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 International 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.