Regulatory effects of Ribosomal S6 Kinase 1 (RSK1) in IFNλ signaling

Barbara Kroczynska, Sonali Joshi, Elizabeth A. Eklund, Amit Verma, Sergei V. Kotenko, Eleanor N. Fish, Leonidas C. Platanias

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Although the mechanisms of generation of signals that control transcriptional activation of Type III IFN (IFNλ)-regulated genes have been identified, very little is known about the mechanisms by which the IFNλ receptor generates signals for mRNA translation of IFNλ-activated genes. We provide evidence that IFNλ activates the p90 ribosomal protein S6 kinase 1 (RSK1) and its downstream effector, initiation factor eIF4B. Prior to its engagement by the IFNλ receptor, the non-active form of RSK1 is present in a complex with the translational repressor 4E-BP1 in IFNλ-sensitive cells. IFNλ-inducible phosphorylation/activation of RSK1 results in its dissociation from 4E-BP1 at the same time that 4E-BP1 dissociates from eIF4E to allow formation of eIF4F and initiation of cap-dependent translation. Our studies demonstrate that such IFNλ-dependent engagement of RSK1 is essential for up-regulation of p21WAF1/CIP1 expression, suggesting a mechanism for generation of growth-inhibitory responses. Altogether, our data provide evidence for a critical role for the activated RSK1 in IFNλ signaling.

Original languageEnglish (US)
Pages (from-to)1147-1156
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number2
DOIs
StatePublished - Jan 14 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kroczynska, B., Joshi, S., Eklund, E. A., Verma, A., Kotenko, S. V., Fish, E. N., & Platanias, L. C. (2011). Regulatory effects of Ribosomal S6 Kinase 1 (RSK1) in IFNλ signaling. Journal of Biological Chemistry, 286(2), 1147-1156. https://doi.org/10.1074/jbc.M110.183566