RRC ID 42876
Author Christakos S, Dhawan P, Peng X, Obukhov AG, Nowycky MC, Benn BS, Zhong Y, Liu Y, Shen Q.
Title New insights into the function and regulation of vitamin D target proteins.
Journal J Steroid Biochem Mol Biol
Abstract 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.
Volume 103(3-5)
Pages 405-10
Published 2007-3
DOI 10.1016/j.jsbmb.2006.12.079
PII S0960-0760(06)00445-6
PMID 17257825
PMC PMC2859311
MeSH Animals Calbindins Calcium / metabolism Cell Line Cholestanetriol 26-Monooxygenase / metabolism Chromatin / genetics Electrophysiology Ion Channel Gating Mutation / genetics Patch-Clamp Techniques Rats Receptors, Calcitriol / metabolism S100 Calcium Binding Protein G / metabolism Vitamin D / metabolism*
IF 3.785
Times Cited 17
Human and Animal Cells