title: CDP/cut is an osteoblastic coactivator of the vitamin D receptor (VDR).
abstract: Vitamin D plays an important role in regulating bone and calcium metabolism. The actions of vitamin D are mediated through the nuclear vitamin D receptor (VDR), and gene disruption of the VDR in mice causes skeletal disorders. However, the precise role of the VDR in each stage of osteoblastogenesis is not well understood. To address this issue, we used a biochemical approach to identify an osteoblast-specific coregulator of the VDR. Using a GST-fused VDR ligand-binding domain as bait, proteins associated with liganded VDR were purified from nuclear extracts of HOS osteoblastic cells and compared with those of HeLa cells. Among the interactants identified by mass fingerprinting, CCAAT displacement protein (CDP) was found as a novel ligand-dependent VDR interactant in HOS cells, together with other previously reported DRIP/TRAP complex components. Further biochemical analysis showed that complex formation between the VDR and CDP was distinct from the previously known DRIP/TRAP complex and the p160 family coactivator complexes. Transient expression of CDP potentiated VDR-mediated transcriptional activation in HOS cells. Furthermore, modulation of CDP expression levels in osteoblastic SaM-1 cells affected vitamin D-dependent osteoblast differentiation before the maturation (mineralization) stage. These findings suggest that CDP is a novel differentiation stage-specific coactivator of the VDR in osteoblasts.
authors.affiliation: Teijin Institute for Bio-Medical Research, Teijin Pharma, Ltd., Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Ochiai
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
authors.forename: Sally
authors.initials: S
authors.lastname: Fujiyama
authors.forename: Shun
authors.initials: S
authors.lastname: Sawatsubashi
authors.forename: Mi-sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mezaki
authors.forename: Yu
authors.initials: Y
authors.lastname: Tsushima
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Takagi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Azuma
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamimura
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: C080632:CUX1 protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D018167:Receptors, Calcitriol; D012097:Repressor Proteins; D014157:Transcription Factors