1alpha,25-dihydroxyvitamin D3 inducible transcription factor and its role in the vitamin D action.
Vitamin D is considered multifunctional steroid hormone that modulates calcium homeostasis through actions predominantly in kidney, bone and the intestinal tract. Nuclear vitamin D receptor (VDR) is a specific nuclear protein, a member of steroid hormone receptor superfamily. The amino acid sequence of the VDR shows a significant homology with other members of the nuclear hormone receptor superfamily, including receptors for glucocorticoids (GR), oestrogen (ER), androgen (AR), progesteron (PR), thyroid hormone (T3R), retinoic acid (RAR), retinoid X (RXR) and over 150 orphan receptors. VDR is known to mediate the pleiotropic biological actions of 1a,25-dihydroxyvitamin D3 through its ability to modulate the expression of target genes. VDR upon binding 1a,25-dihydroxyvitamin D3 regulates specific gene transcription predominantly by binding as a heterodimer with the retinoid X receptor (RXR) to DNA enhancer sequence, termed the vitamin D-responsive element (VDRE) that is present within the promoter region of vitamin D-controlled genes. The VDR has been shown to associate with several additional molecules to form the active transcriptional complex required for gene regulation. The regulation of this ligand-activated cellular transcription factor occurs at both transcriptional and posttranslational levels. This article summarizes a variety of effects of 1a,25-dihydroxyvitamin D3, acting through its cognate nuclear receptor, and its use in chemotherapy and chemoprevention of cancer.
Nezbedova
P
P
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, 833 06 Bratislava, Slovakia.
Brtko
J
J
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000517:prevention & control; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000235:genetics* / Q000378:metabolism*
C116441:2-methyl-1,25-dihydroxyvitamin D3; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014807:Vitamin D