MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation.

ABSTRACT: We isolated MED25, which associates with retinoic acid (RA)-bound retinoic acid receptor (RAR) through the C-terminal nuclear hormone receptor (NR) box/LxxLL motif, and increases RAR/RXR-mediated transcription. When tethered to a promoter, MED25 showed intrinsic transcriptional activity in its PTOV domain, which is likely accomplished by direct association with CBP. Reporter assays using dominant negatives of MED25 demonstrated the importance of the N-terminal Mediator-binding and C-terminal domains in CBP and RAR/RXR binding, which affect MED25 activity. Downregulation of MED25 specifically reduced RAR but not thyroid hormone receptor (TR) activity. Stimulation of RAR by MED25 was correlated with enhanced RA cytotoxicity in vivo. Chromatin immunoprecipitation (ChIP) assays revealed the RA

SUBMITTER: Lee HK 

PROVIDER: S-EPMC1949011 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature