TY - JOUR
T1 - Regulatory effects of Ribosomal S6 Kinase 1 (RSK1) in IFNλ signaling
AU - Kroczynska, Barbara
AU - Joshi, Sonali
AU - Eklund, Elizabeth A.
AU - Verma, Amit
AU - Kotenko, Sergei V.
AU - Fish, Eleanor N.
AU - Platanias, Leonidas C.
PY - 2011/1/14
Y1 - 2011/1/14
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M110.183566
DO - 10.1074/jbc.M110.183566
M3 - Article
C2 - 21075852
AN - SCOPUS:78651397868
SN - 0021-9258
VL - 286
SP - 1147
EP - 1156
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 2
ER -