MCB Accepts, published online ahead of print on 12 February 2007

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Mol. Cell. Biol. doi:10.1128/MCB.02276-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Rev7/MAD2B links JNK pathway signalling to activation of the transcription factor Elk-1

Lin Zhang, Shen-Hsi Yang^*, and Andrew D. Sharrocks

Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK

^* To whom correspondence should be addressed. Email: s.yang{at}manchester.ac.uk.

The MAP kinases represent one of the most important classes of signalling cascades that are used by eukaryotic cells to sense extracellular signals. One of the major responses to these cascades is a change in cellular gene expression profiles mediated through the direct targeting of transcriptional regulators such as the transcription factor Elk-1. Here we have identified hRev7/MAD2B/MAD2L2 as an interaction partner for Elk-1 and demonstrate that hRev7 acts to promote Elk-1 phosphorylation by the JNK MAP kinases. As phosphorylation of Elk-1 potentiates the activity of its TAD, hRev7 therefore contributes to the upregulation of Elk-1 target genes such as egr-1 following exposure of cells to stress conditions caused by DNA damaging agents. Thus, given its previous roles in permitting DNA damage bypass during replication, and regulating cell cycle progression, our data linking hRev7 to gene expression changes suggest that hRev7 has a widespread role in coordinating the cellular response to DNA damage.

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