title: Vitamin D analogs and coactivators.
abstract: The secosteroid hormone 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has potent antiproliferative and prodifferentiating actions on a wide variety of normal as well as malignant cell types. Strong calcemic effects obstruct the actual application of 1,25-(OH)2D3 for the treatment of hyperproliferative disorders such as cancer. To overcome this problem, structural analogs of 1,25-(OH)2D3 have been designed with a clear dissociation between antiproliferative and calcemic effects. This review focuses on the molecular mode of action of different 1,25-(OH)2D3 analogs and, in particular, on the recruitment of cofactor molecules to the vitamin D receptor by these analogs.
authors.affiliation: Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Eelen
authors.forename: Lieve
authors.initials: L
authors.lastname: Verlinden
authors.forename: Pierre
authors.initials: P
authors.lastname: De Clercq
authors.forename: Maurits
authors.initials: M
authors.lastname: Vandewalle
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C491310:GRIP1 protein, human; C498001:NCOA2 protein, human; D009419:Nerve Tissue Proteins; D051958:Nuclear Receptor Coactivator 2; D018167:Receptors, Calcitriol; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538866:NCOA3 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D050880:p300-CBP Transcription Factors; D002117:Calcitriol