PIASx acts as an Elk-1 coactivator by facilitating derepression

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 PIASxα 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. PIASxα binds to Elk-1 in vivo and enhances its transcriptional activity. The coactivating properties of PIASxα require Elk-1 to be modified with SUMO and the integrity of the SUMO binding motif in PIASxα. PIASxα activates Elk-1 through alterations in the HAT/HDAC activities associated with Elk-1. In particular, PIASxα 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 PIASxα through reversing SUMO-mediated repression of transcription factor activity. © 2005 European Molecular Biology Organization | All Rights Reserved.