140: Roles of Rictor/Sin1 complexes in IFN-generated responses

Abstract

There is emerging evidence that mammalian target of Rapamycin (mTOR) complexes play important roles in IFN-signaling and mRNA translation of interferon-stimulated genes (ISGs), by controlling the function of downstream effector pathways. We provide evidence that IFN-induced ISG expression is defective in cells with targeted disruption of the Rictor gene, a key component of the mTORC2 complex. Our studies demonstrate that there is defective expression of several IFN-inducible genes that mediate important biological functions, including anti-proliferative, antiviral and pro-apoptotic responses. Importantly, we also found that Rictor and Sin1 play essential roles in the generation of the suppressive effects of IFN alpha on malignant erythroid precursors from patients with myeloproliferative neoplasms (MPNs), suggesting unique roles for such complexes in the IFN-system. Altogether, our data provide evidence for critical and essential roles for Rictor/Sin1 complexes in IFN-signaling and the control of IFN-responses.