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J Biol Chem. 2011 Jan 14;286(2):1147-56. doi: 10.1074/jbc.M110.183566. Epub 2010 Nov 12.

Regulatory effects of ribosomal S6 kinase 1 (RSK1) in IFNλ signaling.

Author information

1
Division of Hematology-Oncology, Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60611, USA.

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 p21(WAF1/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.

PMID:
21075852
PMCID:
PMC3020721
DOI:
10.1074/jbc.M110.183566
[Indexed for MEDLINE]
Free PMC Article

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