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 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.
Christakos
S
S
Department of Biochemistry, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA. christak@umdnj.edu
Barletta
F
F
Huening
M
M
Dhawan
P
P
Liu
Y
Y
Porta
A
A
Peng
X
X
D000818:Animals; D017209:Apoptosis; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology; D065668:Vitamin D3 24-Hydroxylase
D023081:CCAAT-Binding Factor; D064026:Calbindins; D018167:Receptors, Calcitriol; D064030:S100 Calcium Binding Protein G; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002118:Calcium