SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.

摘要: Inflammation associates with peripheral insulin resistance, which dysregulates nutrient homeostasis and leads to diabetes. induces the expression of SOCS proteins. We show that SOCS1 or SOCS3 targeted IRS1 IRS2, two critical signaling molecules for action, ubiquitin-mediated degradation. bound both recombinant endogenous IRS2 promoted their ubiquitination subsequent degradation in multiple cell types. Mutations conserved box abrogated its interaction elongin BC ubiquitin-ligase complex without affecting binding IRS2. The mutants also failed promote either Adenoviral-mediated mouse liver dramatically reduced hepatic protein levels caused glucose intolerance; by contrast, had no effect. Thus, SOCS-mediated IRS proteins, presumably via ubiquitin-ligase, might be a general mechanism inflammation-induced providing target therapy.