title: Multiple co-activator complexes support ligand-induced transactivation function of VDR.
abstract: Vitamin D receptor (VDR) mediates a wide variety of vitamin D actions through transcriptional controls of target genes as a ligand-dependent transcription factor. The transactivation by VDR is known to associate with two co-activator complexes, DRIP/TRAP and p160/CBP, through physical interaction with DRIP205 and p160 members (TIF2) components, respectively. However, functional difference between the two co-activator complexes for VDR co-activation remains unclear. In the present study, to address this issue, a series of point mutants in VDR helix 12 were generated to test the functional association. Alanine replacement of VDR valine 418 resulted in loss of DRIP205 interaction, but it was still transcriptionally potent with ability to interact with TIF2. Surprisingly, the V421A mutant was only partially impaired in transactivation without co-activator interaction, implying presence of a putative co-activator/complex. Thus, these findings suggest that ligand-induced transcriptional controls by VDR require a number of known and unknown co-regulator complexes, that may support the tissue-specific function of VDR.
authors.affiliation: ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchisi, Saitama 332-0012, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Masayo
authors.initials: M
authors.lastname: Shindo
authors.forename: Kei
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yamaoka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002522:Chlorocebus aethiops; D003345:Corticosterone; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D056913:Mediator Complex Subunit 1; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D007527:Isoenzymes; C538855:MED1 protein, human; D056913:Mediator Complex Subunit 1; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D018167:Receptors, Calcitriol; D014157:Transcription Factors; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D003345:Corticosterone