Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog.
The nuclear vitamin D receptor (VDR) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor. A family of cotranscriptional activators (SRC-1, TIF2, and AIB-1) interacts with and activates the transactivation function of nuclear receptors in a ligand-dependent way. We examined interaction of VDR with these coactivators that was induced by several vitamin D analogs, since they exert differential subsets of the biological action of vitamin D through unknown mechanisms. Unlike other vitamin D analogs tested, OCT (22-oxa-1alpha,25-dihydroxyvitamin D3) induced interaction of VDR with TIF2 but not with SRC-1 or AIB-1. Consistent with these interactions, only TIF2 was able to potentiate the transactivation function of VDR bound to OCT. Thus, the present findings suggest that the structure of VDR is altered in a vitamin D analog-specific way, resulting in selective interactions of VDR with coactivators. Such selective interaction of coactivators with VDR may specify the array of biological actions of a vitamin D analog like OCT, possibly through activating a particular set of target gene promoters.
Takeyama
K
K
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113, Japan.
Masuhiro
Y
Y
Fuse
H
H
Endoh
H
H
Murayama
A
A
Kitanaka
S
S
Suzawa
M
M
Yanagisawa
J
J
Kato
S
S
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002762:Cholecalciferol / Q000378:metabolism; D015342:DNA Probes / Q000235:genetics; D066298:In Vitro Techniques; D008024:Ligands; D009687:Nuclear Proteins / Q000378:metabolism; D051958:Nuclear Receptor Coactivator 2; D011485:Protein Binding; D051381:Rats; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
D015342:DNA Probes; D008024:Ligands; C498003:Ncoa2 protein, rat; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D018167:Receptors, Calcitriol; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014807:Vitamin D; D002762:Cholecalciferol