New insights into the function and regulation of vitamin D target proteins

Sylvia Christakos, Puneet Dhawan, Xiaorong Peng, Alexander G. Obukhov, Martha C. Nowycky, Bryan S. Benn, Yan Zhong, Yan Liu, Qi Shen

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Calbindin-D28k 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-D28k results in reduced calcium influx through voltage-dependent L-type Ca2+ channels and enhanced sensitivity of the channels to calcium dependent inactivation. Co-immunoprecipitation and GST pull down assays indicate that calbindin-D28k interacts with the C-terminus of the L-type calcium channel alpha1c subunit (Cav1.2). 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)2D3 is 24(OH)ase, which is involved in the catabolism of 1,25(OH)2D3. We reported that C/EBPβ 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/EBPβ in regulating 24(OH)ase. These findings define novel mechanisms that may be of fundamental importance in understanding how 1,25(OH)2D3 mediates its multiple biological effects.

Original languageEnglish (US)
Pages (from-to)405-410
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume103
Issue number3-5
DOIs
StatePublished - Mar 2007

Keywords

  • 25-Hydroxyvitamin D3 24-hydroxylase
  • CCAAT enhancer binding protein
  • Calbindin-D
  • L-type calcium channels
  • SWI/SNF chromatin remodeling complex

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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