Eukaryotic Cell
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EC Accepts, published online ahead of print on 26 October 2007
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EC.00327-06v1
6/12/2251    most recent
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Eukaryotic Cell doi:10.1128/EC.00327-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

THE CCR4-NOT COMPLEX REGULATES SKN7 THROUGH THE SRB10 KINASE

Eve Lenssen, Nowel Azzouz, Agnès Michel, Emilie Landrieux, and Martine A. Collart*

Dpt of Microbiology and Molecular Medicine, University of Geneva Medical School, CMU, 1 rue Michel Servet, 1211 Geneva 4, Switzerland

* To whom correspondence should be addressed. Email: martine.collart{at}medecine.unige.ch.


  Abstract

The Ccr4-Not complex is a multifunctional regulatory platform composed of 9 subunits that controls diverse cellular events including mRNA degradation, protein ubiquitination, and transcription. In this study, we identified the yeast Saccharomyces cerevisiae osmotic and oxidative stress transcription factor Skn7, as a new target for regulation by the Ccr4-Not complex. Skn7 interacts with Not1 in a two-hybrid assay and co-immunoprecipitates with Not5 in a Not4-dependent manner. Skn7-dependent expression of OCH1 and Skn7 binding to the OCH1 promoter are increased in not4{Delta} or not5{Delta} mutants. Skn7 purified from wild-type cells but not from not4{Delta} cells is associated with the Srb10 kinase. This kinase plays a central role in the regulation of Skn7 by Not4, since increased OCH1 expression in not4{Delta} cells requires Srb10. These results reveal a critical role for the Ccr4-Not complex in the mechanism of activation of Skn7 that is dependent upon the Srb10 kinase.


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