Central role of ULK1 in type I interferon signaling Journal Article

Authors: Saleiro, D.; Mehrotra, S.; Kroczynska, B.; Beauchamp, E. M.; Lisowski, P.; Majchrzak-Kita, B.; Bhagat, T. D.; Stein, B. L.; McMahon, B.; Altman, J. K.; Kosciuczuk, E. M.; Baker, D. P.; Jie, C.; Jafari, N.; Thompson, C. B.; Levine, R. L.; Fish, E. N.; Verma, A. K.; Platanias, L. C.
Article Title: Central role of ULK1 in type I interferon signaling
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 ofULK1 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 ofantineoplastic responses. © 2015 The Authors.
Keywords: signal transduction; controlled study; unclassified drug; human cell; interferon; nonhuman; alpha interferon; protein function; animal cell; mouse; erythroid precursor cell; embryo; genetic transcription; enzyme activation; in vitro study; gene expression regulation; enzyme phosphorylation; transcription regulation; tumor immunity; dna structure; phosphotransferase; unc 51 like kinase 1; beta interferon; interferon receptor; myeloproliferative neoplasm; virus immunity; mitogen activated protein kinase 14; human; priority journal; article; unc 51 like kinase 2; encephalitis virus; gamma interferon activation site; interferon stimulated response elements
Journal Title: Cell Reports
Volume: 11
Issue: 4
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2015-04-28
Start Page: 605
End Page: 617
Language: English
DOI: 10.1016/j.celrep.2015.03.056
PROVIDER: scopus
PUBMED: 25892232
PMCID: PMC4477687
Notes: Export Date: 3 June 2015 -- Source: Scopus
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MSK Authors
  1. Ross Levine
    508 Levine
  2. Craig Bernie Thompson
    122 Thompson