Coactivator ASC-2 mediates heat shock factor 1-mediated transactivation dependent on heat shock
Abstract
Upon exposure to elevated temperatures, mammalian cells increase the expression of the heat shock proteins (HSP) through activation of the heat shock factor 1 (HSF1). Since most transcription factors require coactivators for efficient transcriptional activity, we tried to identify the coactivator(s) that interacts with and modulates the activities of HSF1. In vitro glutathione S-transferase (GST) pull-down assay revealed that HSF1 strongly interacts with activating signal cointegrator (ASC)-2 and weakly with cyclic adenosine monophosphate responsive element binding protein (CBP). We also show that cotransfection of ASC-2, but not CBP, potentiates HSF1-mediated transactivation based on its cognate element (heat shock element, HSE) linked to luciferase reporter. The molecular interaction of HSF1 and ASC-2 was stimulated by heat shock in cells and the overexpression of HSF1-interacting domain of ASC-2 inhibited the specific induced protein association and HSF1-mediated transactivation. Taking these results together, we suggest that ASC-2 in a novel coactivator for HSF1 and heat shock stress may contribute the strong active transcription complex through sequential recruitment of HSF1 and ASC-2.
- Publication:
-
FEBS Letters
- Pub Date:
- January 2004
- DOI:
- 10.1016/S0014-5793(04)00028-6
- Bibcode:
- 2004FEBSL.559..165H
- Keywords:
-
- HSF-1;
- ASC-2;
- Heat shock;
- Transactivation;
- HSP;
- heat shock protein;
- HSF;
- heat shock factor;
- CBP;
- cyclic adenosine monophosphate responsive element binding protein;
- ERK;
- extracellular regulated kinase;
- ASC;
- activating signal cointegrator;
- SDS–PAGE;
- sodium dodecyl sulfate–polyacrylamide gel electrophoresis;
- GST;
- glutathione S-transferase