Vitamin D target proteins: Function and regulation

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 β cells, a cause of insulin dependent diabetes, is also inhibited by calbindin‐D 28k . In calbindin‐D 28k transfected pancreatic β 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 β (C/EBPβ) 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/EBPβ as a novel 1,25(OH) 2 D 3 target gene and indicate a role for C/EBPβ 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. J. Cell. Biochem. 88: 238–244, 2003. © 2002 Wiley‐Liss, Inc.