New insights into the function and regulation of vitamin D target proteins.
Calbindin-D(28k) has been reported to be a facilitator of calcium diffusion and to protect against apoptotic cell death. Most recently, we found that the presence of calbindin-D(28k) results in reduced calcium influx through voltage-dependent L-type Ca(2+) channels and enhanced sensitivity of the channels to calcium dependent inactivation. Co-immunoprecipitation and GST pull down assays indicate that calbindin-D(28k) interacts with the C-terminus of the L-type calcium channel alpha(1c) subunit (Ca(v)1.2). This is the first report of the binding of calbindin to a calcium channel and provides new insight concerning mechanisms by which calbindin acts to modulate intracellular calcium. Besides calbindin, another major target of 1,25(OH)(2)D(3) is 24(OH)ase, which is involved in the catabolism of 1,25(OH)(2)D(3). We reported that C/EBPbeta is a major transcriptional activator of 24(OH)ase that cooperates with CBP/p300 in regulating VDR mediated 24(OH)ase transcription. Recently, we found, in addition to p160 coactivators, that SWI/SNF complexes (that facilitate transcription by remodeling chromatin using the energy of ATP hydrolysis) are also involved in VDR mediated 24(OH)ase transcription and functionally cooperate with C/EBPbeta in regulating 24(OH)ase. These findings define novel mechanisms that may be of fundamental importance in understanding how 1,25(OH)(2)D(3) mediates its multiple biological effects.
Christakos
Sylvia
S
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. christak@umdnj.edu
Dhawan
Puneet
P
Peng
Xiaorong
X
Obukhov
Alexander G
AG
Nowycky
Martha C
MC
Benn
Bryan S
BS
Zhong
Yan
Y
Liu
Yan
Y
Shen
Qi
Q
D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D053493:Cholestanetriol 26-Monooxygenase / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D004594:Electrophysiology; D015640:Ion Channel Gating; D009154:Mutation / Q000235:genetics; D018408:Patch-Clamp Techniques; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*
D064026:Calbindins; D002843:Chromatin; D018167:Receptors, Calcitriol; D064030:S100 Calcium Binding Protein G; D014807:Vitamin D; D053493:Cholestanetriol 26-Monooxygenase; D002118:Calcium