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| Subject Categories: Chromatin & Transcription | Proteins |
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| The EMBO Journal
(2005) 24, 2161–2171, doi:10.1038/sj.emboj.7600690 Published online 26 May 2005 |
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| PIASx acts as an Elk-1 coactivator by facilitating derepression |
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| Shen-Hsi Yang and Andrew D Sharrocks |
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Faculty of Life Sciences, University of Manchester, Manchester, UK To whom correspondence should be addressed Andrew D Sharrocks, Faculty of Life Sciences, University of Manchester, Michael Smith building, Oxford Road, Manchester M13 9PT, UK. Tel.: +44 161 275 5979; Fax: +44 161 275 5082; E-mail: a.d.sharrocks@manchester.ac.uk Received 2 February 2005; Accepted 2 May 2005; Published online 26 May 2005. |
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| Abstract |
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The ETS-domain transcription factor Elk-1 is a MAP kinase-inducible transcriptional activator protein. However, in the basal state, its activity is repressed by SUMO-dependent histone deacetylase (HDAC) recruitment. Relief of this repression accompanies the activation process. Here, we demonstrate that PIASx acts to facilitate this derepression process. Members of the PIAS family of proteins can act as E3 enzymes that enhance the sumoylation status of a variety of substrates. However, PIASx-mediated coactivation of Elk-1 occurs in an E3 activity-independent manner. PIASx binds to Elk-1 in vivo and enhances its transcriptional activity. The coactivating properties of PIASx require Elk-1 to be modified with SUMO and the integrity of the SUMO binding motif in PIASx. PIASx activates Elk-1 through alterations in the HAT/HDAC activities associated with Elk-1. In particular, PIASx facilitates the loss of the repressive HDAC-2 from sumoylated Elk-1, a key event in the activation of Elk-1 in response to signalling through the ERK MAP kinase pathway. Our data therefore reveal a novel coactivator function for PIASx through reversing SUMO-mediated repression of transcription factor activity. |
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| Keywords: Elk-1, HDAC-2, PIAS, SUMO, transcriptional coactivator |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHAn extended consensus motif enhances the specificity of substrate modification by SUMO The EMBO Journal Article (01 Nov 2006) An extended consensus motif enhances the specificity of substrate modification by SUMO The EMBO Journal Article |
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