期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 304, 期 4, 页码 632-637出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0006-291X(03)00651-X
关键词
VDR; gene repression; nVDRE; DNA-PK; Wortmannin; nuclear hormone receptor; Ku
The mechanism of transcriptional repression by nuclear hormone receptors, especially in the presence of the ligands, is largely unknown. We previously reported that 1,25-dihydroxyvitaminD(3) (1,25 vitaminD(3)) inhibited expression of the parathyroid hormone-related polypeptide (PTHrP) gene through the interaction between the liganded monomeric vitamin D receptor (VDR) and the negative DNA element in the PTHrP gene (nVDRE(RP)). In this study, we employed chromatin immunoprecipitation (ChIP) assay and confirmed that 1,25 vitaminD(3) recruited DNA-dependent protein kinase (DNA-PKcs) to the chromatinized nVDRE(RP). Conversely, the regulatory subunits of DNA-PK were associated with the nVDRE(RP) sequences only when 1,25 vitaminD(3) was absent. VDR was constitutively associated with these chromatinized nVDRERP sequences. Furthermore, DNA-PKcs could phosphorylate VDR in vitro. We raise a possibility that a conformational change of VDR through its phosphorylation mediated by DNA-PKcs underlies the mechanism of gene repression by 1,25 vitaminD(3)-bound VDR. (C) 2003 Elsevier Science (USA). All rights reserved.
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