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Published on: June 28, 2011
TORCs: transducers of regulated CREB activity
Michael D Conkright1, Gianluca Canettieri, Robert Screaton
1The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Molecular Cell
|October 11, 2003
Summary
Researchers identified Transducers of Regulated CREB activity (TORCs) that enhance CREB-dependent gene expression through a novel interaction. This discovery sheds light on CREB
Area of Science:
- Molecular Biology
- Gene Regulation
- Cancer Biology
Background:
- CREB (cAMP responsive element-binding protein) is a transcription factor that stimulates gene expression upon phosphorylation.
- The mechanisms underlying CREB's constitutive activation in certain cell types remain unclear.
- CBP is a known coactivator for phosphorylated CREB.
Purpose of the Study:
- To characterize a novel family of coactivators for CREB, termed TORCs (Transducers of Regulated CREB activity).
- To elucidate the mechanism by which TORCs enhance CRE-dependent transcription.
- To investigate the role of TORCs in cancer, specifically mucoepidermoid carcinomas.
Main Methods:
- Co-immunoprecipitation assays to study protein interactions.
- Reporter gene assays to measure transcriptional activity.
- Analysis of a specific chromosomal translocation in mucoepidermoid carcinomas involving TORC1 and MAML2.
Main Results:
- TORCs enhance CRE-dependent transcription through a phosphorylation-independent interaction with CREB's DNA binding domain.
- TORC recruitment enhances CREB's interaction with TFIID's TAF(II)130 component.
- A TORC1-MAML2 fusion protein (chimera) was identified in mucoepidermoid carcinomas and strongly induced target gene expression.
Conclusions:
- TORCs represent a novel class of CREB coactivators that function independently of CREB phosphorylation.
- TORCs enhance CREB transcriptional activity by facilitating interactions with the TFIID complex.
- The TORC1-MAML2 fusion protein highlights a mechanism for aberrant CREB activation in cancer.
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