Emerging insights into the coactivator role of NCoA62/SKIP in Vitamin D-mediated transcription.
NCoA62/SKIP was discovered as a nuclear protein that interacts with the Vitamin D receptor (VDR) and the SKI oncoprotein. NCoA62/SKIP expresses properties consistent with other nuclear receptor transcriptional coactivator proteins. For example, NCoA62/SKIP interacts selectively with the VDR-RXR heterodimer, it forms a ternary complex with liganded VDR and steroid receptor coactivator (SRC) proteins, and it synergizes with SRCs to augment 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)]- and VDR-activated transcription. Chromatin immunoprecipitation studies show that NCoA62/SKIP is recruited in a 1,25-(OH)(2)D(3)-dependent manner to native Vitamin D responsive gene promoters and it enters these promoter complexes after VDR and SRC entry. This suggests that NCoA62/SKIP functions at a distal step in the transactivation process. Recent studies indicate that NCoA62/SKIP is a component of the spliceosome machinery and interacts with important splicing factors such as prp8 and the U5 200kDa helicase. Functional studies also support an involvement of NCoA62/SKIP in mRNA splicing. Collectively, these data suggest a pivotal role for NCoA62/SKIP in coupling transcriptional regulation by VDR to RNA splicing. They further solidify an important role for VDR/NR-interactors downstream of the transcription process in determining the overall response of Vitamin D and steroid hormone regulated genes.
MacDonald
Paul N
PN
Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. pnm2@po.cwru.edu
Dowd
Diane R
DR
Zhang
Chi
C
Gu
Chun
C
D000818:Animals; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D056918:Nuclear Receptor Coactivators; D014157:Transcription Factors; D014158:Transcription, Genetic; D014807:Vitamin D / Q000494:pharmacology*
D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; C111791:SNW1 protein, human; D014157:Transcription Factors; D014807:Vitamin D