Signal Transduction of Type 1 Interferons in Malignant Cells

Interferons (IFNs) exhibit important antitumor effects in vitro and in vivo and play key roles in the immune surveillance against cancer. We have identified a novel signaling mechanism activated by the Type I IFN receptor, involving the kinase ULK1. This IFN-controlled signaling cascade is unrelated to the effects of ULK1 on autophagy and was previously unknown. The proposal will precisely define the role of ULK1 signals in the induction of the biological effects of IFNs in myeloproliferative neoplasms (MPNs) and will identify upstream and downstream effectors of the pathway. Ultimately, the studies of this proposal can lead to the development of novel approaches for the treatment of MPNs and other malignancies.