Stress induced gene expression : a direct role for MAPKAP kinases in transcriptional activation of immediate early genes. / Ronkina, N.; Menon, M. B.; Schwermann, J.; Arthur, J. S. C.; Legault, H.; Telliez, J. -B.; Kayyali, U. S.; Nebreda, A. R.; Kotlyarov, A.; Gaestel, M.
In: Nucleic Acids Research, Vol. 39, No. 7, 04.2011, p. 2503-2518.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stress induced gene expression
T2 - a direct role for MAPKAP kinases in transcriptional activation of immediate early genes
A1 - Ronkina,N.
A1 - Menon,M. B.
A1 - Schwermann,J.
A1 - Arthur,J. S. C.
A1 - Legault,H.
A1 - Telliez,J. -B.
A1 - Kayyali,U. S.
A1 - Nebreda,A. R.
A1 - Kotlyarov,A.
A1 - Gaestel,M.
AU - Ronkina,N.
AU - Menon,M. B.
AU - Schwermann,J.
AU - Arthur,J. S. C.
AU - Legault,H.
AU - Telliez,J. -B.
AU - Kayyali,U. S.
AU - Nebreda,A. R.
AU - Kotlyarov,A.
AU - Gaestel,M.
PY - 2011/4
Y1 - 2011/4
N2 - <p>Immediate early gene (IEG) expression is coordinated by multiple MAP kinase signaling pathways in a signal specific manner. Stress-activated p38 alpha MAP kinase is implicated in transcriptional regulation of IEGs via MSK-mediated CREB phosphorylation. The protein kinases downstream to p38, MAPKAP kinase (MK) 2 and MK3 have been identified to regulate gene expression at the posttranscriptional levels of mRNA stability and translation. Here, we analyzed stress-induced IEG expression in MK2/3-deficient cells. Ablation of MKs causes a decrease of p38 alpha level and p38-dependent IEG expression. Unexpectedly, restoration of p38 alpha does not rescue the full-range IEG response. Instead, the catalytic activity of MKs is necessary for the major transcriptional activation of IEGs. By transcriptomics, we identified MK2-regulated genes and recognized the serum response element (SRE) as a common promoter element. We show that stress-induced phosphorylation of serum response factor (SRF) at serine residue 103 is significantly reduced and that induction of SRE-dependent reporter activity is impaired and can only be rescued by catalytically active MK2 in MK2/3-deficient cells. Hence, a new function of MKs in transcriptional activation of IEGs via the p38 alpha-MK2/3-SRF-axis is proposed which probably cooperates with MKs' role in posttranscriptional gene expression in inflammation and stress response.</p>
AB - <p>Immediate early gene (IEG) expression is coordinated by multiple MAP kinase signaling pathways in a signal specific manner. Stress-activated p38 alpha MAP kinase is implicated in transcriptional regulation of IEGs via MSK-mediated CREB phosphorylation. The protein kinases downstream to p38, MAPKAP kinase (MK) 2 and MK3 have been identified to regulate gene expression at the posttranscriptional levels of mRNA stability and translation. Here, we analyzed stress-induced IEG expression in MK2/3-deficient cells. Ablation of MKs causes a decrease of p38 alpha level and p38-dependent IEG expression. Unexpectedly, restoration of p38 alpha does not rescue the full-range IEG response. Instead, the catalytic activity of MKs is necessary for the major transcriptional activation of IEGs. By transcriptomics, we identified MK2-regulated genes and recognized the serum response element (SRE) as a common promoter element. We show that stress-induced phosphorylation of serum response factor (SRF) at serine residue 103 is significantly reduced and that induction of SRE-dependent reporter activity is impaired and can only be rescued by catalytically active MK2 in MK2/3-deficient cells. Hence, a new function of MKs in transcriptional activation of IEGs via the p38 alpha-MK2/3-SRF-axis is proposed which probably cooperates with MKs' role in posttranscriptional gene expression in inflammation and stress response.</p>
U2 - 10.1093/nar/gkq1178
DO - 10.1093/nar/gkq1178
M1 - Article
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 7
VL - 39
SP - 2503
EP - 2518
ER -