Vitamin D target proteins: Function and regulation

✍ Scribed by S. Christakos; F. Barletta; M. Huening; P. Dhawan; Y. Liu; A. Porta; X. Peng

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 171 KB
• Volume: 88
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10349

✦ Synopsis

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 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.