Back
Acta Physiologica 2007; Volume 189, Supplement 653
The 86th Annual Meeting of The German Physiological Society
3/25/2007-3/28/2007
Hannover, Germany
THE P38A/B MAP KINASES MEDIATE RECRUITMENT OF CBP TO PRESERVE FAST MHCIID/X GENE ACTIVITY IN MYOTUBES
Abstract number: O13-1
Meissner1,2 JD, Chang1,3 KC, Nebreda1,4 AR, Gros1 G, Scheibe1,5 RJ
1Department of Physiology, Hannover Medical School
2JDM,GG,RJS Dept. of Physiology, Hannover Medical School,
3KCC Division of Animal Production & Public Health, Univ. of Glasgow Veterinary School,
4ARN Spanish National Cancer Centre,
5RJS Department of Biochem., Hannover Medical School
Treatment of C2C12 myotubes with Ca2+ -ionophore inhibited p38a/b MAPKs and reduced fast fiber type MHCIId/x promoter activity. In controls, MEF-2 isoforms C and D bind as heterodimer to a proximal consensus site within the promoter and recruit transcriptional coactivator CBP. Overexpressed wildtype MEF-2C but not a mutant deficient in a p38 phosphorylation site induced promoter activity. Mutation of the MEF-2 binding site decreased the inducing effect of CBP. Pharmacological inhibition of p38a/b MAPKs also downregulated the promoter and abolished CBP binding while enforced induction of p38 by activated MAPK kinase 6 (MKK6EE) enhanced binding of CBP and increased promoter activity. In addition, CBP RNAi abolished promoter activation by MEF-2C or MKK6EE. In Ca2+ - ionophore-treated myotubes, CBP was absent in complex formation at the MEF2-site. The data demonstrate the importance of p38a/b MAPKs-mediated coactivator recruitment at a proximal MEF-2 site for MHCIId/x gene regulation in myotubes.
Supported by DFG grants GR489/13 and -20.
To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 189, Supplement 653 :O13-1