Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in vitamin D receptor transactivation during keratinocyte differentiation Journal Article
| Authors: | Oda, Y.; Sihlbom, C.; Chalkley, R. J.; Huang, L.; Rachez, C.; Chang, C. P. B.; Burlingame, A. L.; Freedman, L. P.; Bikle, D. D. |
| Article Title: | Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in vitamin D receptor 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 VDR. However, the relationship between these two classes of coactivators is not clear. Using glutathione-S-transferase-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 DRIP and SRC proteins were expressed in keratinocytes. DRIP205 expression decreased during differentiation, although SRC-3 levels increased. 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 sequentially 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. |
| Keywords: | protein expression; unclassified drug; gene sequence; human cell; cell proliferation; mass spectrometry; protein analysis; cells, cultured; protein; protein binding; cell differentiation; calcitriol; cell line, tumor; protein tyrosine kinase; keratinocyte; transcription factors; nuclear proteins; gene expression regulation; amino acid sequence; molecular sequence data; infant, newborn; vitamin d; transactivation; glutathione transferase; gene control; trans-activators; protein subunit; steroid receptor coactivator 1; vitamin d receptor; keratinocytes; molecular weight; receptor binding; protein p160; protein kinase p60; trans-activation (genetics); histone acetyltransferases; receptors, calcitriol; humans; human; male; priority journal; article; src homology domain; vitamin d receptor interacting protein |
| Journal Title: | Molecular Endocrinology |
| Volume: | 17 |
| Issue: | 11 |
| ISSN: | 0888-8809 |
| Publisher: | Endocrine Society |
| Date Published: | 2003-11-01 |
| Start Page: | 2329 |
| End Page: | 2339 |
| Language: | English |
| DOI: | 10.1210/me.2003-0063 |
| PUBMED: | 12893881 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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