Emerging insights into the coactivator role of NCoA62/SKIP in Vitamin D-mediated transcription

• Published in: Journal of steroid biochemistry and molecular biology Vol. 89; no. 1-5; pp. 179 - 186
• Main Authors: MacDonald, Paul N., Dowd, Diane R., Zhang, Chi, Gu, Chun
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2004; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Cholecalciferol; Coactivator; Fundamental and applied biological sciences. Psychology; Humans; mRNA splicing; NCoA62; Nuclear Proteins - physiology; Nuclear receptor; Nuclear Receptor Coactivators; Ski interacting protein; Transcription Factors; Transcription splicing coupling; Transcription, Genetic; Vertebrates: endocrinology; Vitamin D - pharmacology; Vitamin D receptor; Nuclear receptor; mRNA splicing; Vitamin D receptor; Cholecalciferol; Coactivator; Transcription splicing coupling; NCoA62; Ski interacting protein; Splicing; Transcription; Protein; Messenger RNA; Vitamin D; Colecalciferol; Biological receptor
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2004.03.097

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) 2D 3]- and VDR-activated transcription. Chromatin immunoprecipitation studies show that NCoA62/SKIP is recruited in a 1,25-(OH) 2D 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 200 kDa 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.