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Central role of ULK1 in type I interferon signaling

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Item Type:Article
Title:Central role of ULK1 in type I interferon signaling
Creators Name:Saleiro, D. and Mehrotra, S. and Kroczynska, B. and Beauchamp, E.M. and Lisowski, P. and Majchrzak-Kita, B. and Bhagat, T.D. and Stein, B.L. and McMahon, B. and Altman, J.K. and Kosciuczuk, E.M. and Baker, D.P. and Jie, C. and Jafari, N. and Thompson, C.B. and Levine, R.L. and Fish, E.N. and Verma, A.K. and Platanias, L.C.
Abstract:We provide evidence that the Unc-51-like kinase 1 (ULK1) is activated during engagement of the type I interferon (IFN) receptor (IFNR). Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE) and IFNγ activation site (GAS) elements and controls expression of key IFN-stimulated genes (ISGs). We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK) and establish that the regulatory effects of ULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway. Importantly, we demonstrate that ULK1 is essential for antiproliferative responses and type I IFN-induced antineoplastic effects against malignant erythroid precursors from patients with myeloproliferative neoplasms. Together, these data reveal a role for ULK1 as a key mediator of type I IFNR-generated signals that control gene transcription and induction of antineoplastic responses.
Keywords:Cultured Cells, Erythroid Cells, Interferon Regulatory Factors, Interferon Type I, Intracellular Signaling Peptides and Proteins, MAP Kinase Signaling System, Myeloproliferative Disorders, Neoplastic Gene Expression Regulation, Protein-Serine-Threonine Kinases, Response Elements, Tumor Cell Line, p38 Mitogen-Activated Protein Kinases
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:605-617
Date:28 April 2015
Official Publication:https://doi.org/10.1016/j.celrep.2015.03.056
PubMed:View item in PubMed

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