A transcriptional corepressor, which interacts with hormone receptors of the nucleus, and its applications

摘要

In accordance with the present invention, there are provided novel receptor interacting factors, referred to herein as 'SMRT', i.e., a Silencing Mediator (co-repressor) for Retionic Acid Receptor (RAR) and Thyroid hormone Receptor (TR). SMRT is anovel protein whose association with RAR and TR both in solution and on DNA response elements is destabilized by ligand. The interaction of SMRT with mutant receptors correlates with the transcriptional silencing activites of receptors. in vivo, SMRT functions as a potent co-repressor. A GAL4 DNA binding domain (DBD) fusion of SMRT behaves as a frank repressor of a GAL4-dependent reporter. Together, these data identify a novel class of cofactor which is believed to represent an important mediator of hormone action.