Central Role of ULK1 in Type I Interferon Signaling

Diana Saleiro, Swarna Mehrotra, Barbara Kroczynska, Elspeth M. Beauchamp, Pawel Lisowski, Beata Majchrzak-Kita, Tushar D. Bhagat, Brady L. Stein, Brandon McMahon, Jessica K. Altman, Ewa M. Kosciuczuk, Darren P. Baker, Chunfa Jie, Nadereh Jafari, Craig B. Thompson, Ross L. Levine, Eleanor N. Fish, Amit K. Verma, Leonidas C. Platanias

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)605-617
Number of pages13
JournalCell Reports
Volume11
Issue number4
DOIs
StatePublished - Apr 28 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    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. (2015). Central Role of ULK1 in Type I Interferon Signaling. Cell Reports, 11(4), 605-617. https://doi.org/10.1016/j.celrep.2015.03.056