Vitamin D target proteins: function and regulation.

Abstract

Recent findings have indicated that calbindin-D(28k), the first known target of vitamin D action, is present in osteoblasts and protects against TNF and glucocorticoid induced apoptosis of osteoblastic cells. Cytokine mediated destruction of pancreatic beta cells, a cause of insulin dependent diabetes, is also inhibited by calbindin-D(28k). In calbindin-D(28k) transfected pancreatic beta cells free radical formation by cytokines is inhibited by calbindin. Thus, besides its role as a facilitator of calcium diffusion, calbindin has a major role in protecting against cellular degeneration in different cell types. Besides calbindin, the other known pronounced effect of 1,25(OH)(2)D(3) in intestine and kidney is increased synthesis of 25(OH)D(3) 24-hydroxylase (24(OH)ase) which is involved in the catabolism of 1,25(OH)(2)D(3). We have noted that CCAAT enhancer binding protein beta (C/EBPbeta) is induced by 1,25(OH)(2)D(3) in kidney and osteoblastic cells and can enhance the transcriptional response of 24(OH)ase to 1,25(OH)(2)D(3). These studies establish C/EBPbeta as a novel 1,25(OH)(2)D(3) target gene and indicate a role for C/EBPbeta in 24(OH)ase transcription. These studies extend our previous studies related to factors that affect vitamin D receptor (VDR) mediated 24(OH)ase transcription (YY1, TFIIB, CBP) and the effect of signaling pathways on 24(OH)ase transcription and cofactor recruitment.