Central Role of ULK1 in Type I Interferon Signaling

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2015 Apr 21

PMID 25892232

Citations 46

Authors

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

Affiliations

Soon will be listed here.

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.

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