Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in VDR transactivation during keratinocyte differentiation Journal Article


Authors: Oda, Y.; Sihlbom, C.; Chalkley, R. J.; Huang, L.; Rachez, C.; Chang, C.; Burlingame, A. L.; Freedman, L. P.; Bikle, D. D.
Article Title: Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in VDR transactivation during keratinocyte differentiation
Abstract: Cell programs such as proliferation and differentiation involve the sequential activation and repression of gene expression. Vitamin D, via its active metabolite 1,25-dihydroxyvitamin D (1,25(OH) 2D 3), controls the proliferation and differentiation of a number of cell types, including keratinocytes, by directly regulating transcription. Two classes of coactivators, the Vitamin D receptor (VDR) interacting proteins (DRIP/mediator) and the p160 steroid receptor coactivator family (SRC/p160), control the actions of nuclear hormone receptors, including the Vitamin D receptor. However, the relationship between these two classes of coactivators is not clear. Using GST-VDR affinity beads, we have identified the DRIP/mediator complex as the major VDR binding complex in proliferating keratinocytes. After the cells differentiated, members of the SRC/p160 family were identified in the complex but not major DRIP subunits. Both DRIP205 and SRC-3 potentiated Vitamin D-induced transcription in proliferating cells, but during differentiation, DRIP205 was no longer effective. These results indicate that these two distinct coactivators are differentially involved in Vitamin D regulation of gene transcription during keratinocyte differentiation, suggesting that these coactivators are part of the means by which the temporal sequence of gene expression is regulated during the differentiation process. © 2004 Elsevier Ltd. All rights reserved.
Keywords: controlled study; unclassified drug; human cell; conference paper; binding affinity; protein function; cell proliferation; animals; complex formation; gene expression; protein; cell differentiation; protein tyrosine kinase; proteomics; keratinocyte; cell type; transcription factors; nuclear proteins; gene expression regulation; transcription regulation; transactivation; transcription; rats; trans-activators; hormone receptor; vitamin d receptor; keratinocytes; spectrometry, mass, matrix-assisted laser desorption-ionization; mediator; coactivator; trans-activation (genetics); receptors, calcitriol; human; protein coactivator; protein p160 steroid receptor; vitamin d receptor interacting protein
Journal Title: Journal of Steroid Biochemistry and Molecular Biology
Volume: 89-90
ISSN: 0960-0760
Publisher: Pergamon-Elsevier Science Ltd  
Date Published: 2004-05-01
Start Page: 273
End Page: 276
Language: English
DOI: 10.1016/j.jsbmb.2004.03.106
PROVIDER: scopus
PUBMED: 15225784
DOI/URL:
Notes: Presented at the 12th Workshop on Vitamin D; 2003 Jul 6-10; Maastricht, Netherlands -- Cited By (since 1996):11 -- Export Date: 16 June 2014 -- CODEN: JSBBE -- Source: Scopus
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  1. Christophe Rachez
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  2. Chao-Pei   Chang
    8 Chang