title: Differential regulation of vitamin D receptor (VDR) by the p53 Family: p73-dependent induction of VDR upon DNA damage.
abstract: p63 and p73, members of the p53 family, have been shown to be functionally distinct from p53. Vitamin D receptor (VDR) is a ligand (vitamin D(3))-dependent transcription factor, which is shown to play a major role in calcium homeostasis and keratinocyte differentiation. Vitamin D and its analogues in combination with DNA-damaging agents are extensively used for cancer chemotherapy. In this report, we examined whether p53 affects p63-mediated induction of VDR and studied the effect of DNA damage on VDR induction in p53 null cell lines. Our results demonstrate that p53 itself does not induce VDR expression, nor does it affect p63-mediated VDR induction in the cell lines tested in this study. Furthermore, we observed p53-independent activation of VDR upon DNA damage and associated the induction of VDR to p73. We have demonstrated that ectopic expression of various p73 isoforms can induce VDR expression. Inhibition of p73 in cells treated with DNA-damaging agents exhibited decreased VDR expression. Finally, we show that upon DNA damage, induction of VDR sensitizes the cells to vitamin D treatment. In conclusion, our results indicate that VDR is regulated by p63 and p73 and that the induction of VDR expression upon DNA damage is p73-dependent.
authors: Department of Biochemistry and Molecular Biology, Wright State University, Dayton, Ohio 45435, USA.
authors: Ramakrishna
authors: R
authors: Kommagani
authors: Vandana
authors: V
authors: Payal
authors: Madhavi P
authors: MP
authors: Kadakia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D018167:Receptors, Calcitriol; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
references: Recent Results Cancer Res. 2003;164:83-98
references: 12899515
references: Genes Dev. 2004 Dec 15;18(24):3041-54
references: 15601819
references: Mol Cell Biochem. 2000 May;208(1-2):157-62
references: 10939640
references: Cancer Res. 2005 Feb 1;65(3):758-66
references: 15705872
references: Front Biosci. 2005;10:2723-49
references: 15970529
references: EMBO J. 2005 Jul 6;24(13):2458-71
references: 15944736
references: Cancer Sci. 2005 Nov;96(11):729-37
references: 16271066
references: Cancer Biol Ther. 2005 Nov;4(11):1178-85
references: 16294021
references: Cancer Res. 2006 May 1;66(9):4574-83
references: 16651407
references: Oncogene. 2006 Jun 22;25(26):3745-51
references: 16462763
references: Ann N Y Acad Sci. 2006 Apr;1068:204-13
references: 16831920
references: Anticancer Res. 2006 Jul-Aug;26(4A):2531-42
references: 16886661
references: Expert Opin Ther Targets. 2006 Oct;10(5):735-48
references: 16981830
references: Mol Cancer Res. 2006 Oct;4(10):759-68
references: 17050669
references: J Invest Dermatol. 2007 Apr;127(4):874-80
references: 17082781
references: Oncogene. 2007 Apr 2;26(15):2220-5
references: 17401431
references: Nucleic Acids Res. 2007;35(6):2093-104
references: 17344317
references: Oncogene. 2007 Aug 9;26(36):5169-83
references: 17334395
references: Nature. 2000 Oct 5;407(6804):642-5
references: 11034214
references: Oncogene. 2000 Oct 19;19(44):5091-7
references: 11042697
references: Steroids. 2001 Mar-May;66(3-5):433-40
references: 11179752
references: Mol Cell Biol. 2001 Mar;21(5):1874-87
references: 11238924
references: Oncogene. 2001 Feb 8;20(6):769-74
references: 11314010
references: J Cell Biol. 2001 Jul 23;154(2):369-87
references: 11470825
references: Biochem Soc Trans. 2001 Nov;29(Pt 6):684-8
references: 11709054
references: Mol Cell. 2002 Jan;9(1):175-86
references: 11804596
references: Cell Death Differ. 2002 Mar;9(3):246-51
references: 11859407
references: Nature. 2002 Apr 4;416(6880):560-4
references: 11932750
references: Oncogene. 2002 Apr 11;21(16):2455-65
references: 11971180
references: FEBS Lett. 2002 Jul 3;522(1-3):161-7
references: 12095638
references: FEBS Lett. 2002 Aug 14;525(1-3):93-9
references: 12163168
references: Mol Cancer Ther. 2002 Aug;1(10):821-9
references: 12492115
references: Mol Cell Biol. 2003 Apr;23(7):2264-76
references: 12640112
references: Cancer Cell. 2003 Apr;3(4):403-10
references: 12726865
references: Mol Cell Biochem. 2003 Nov;253(1-2):247-54
references: 14619976
references: Cell Mol Life Sci. 2004 Apr;61(7-8):822-42
references: 15095006
references: Endocr Regul. 2004 Mar;38(1):29-38
references: 15147236
references: Mol Cancer Res. 2004 Jul;2(7):371-86
references: 15280445
references: Cancer Res. 2004 Oct 15;64(20):7447-54
references: 15492269
references: Cell. 1997 Aug 22;90(4):809-19
references: 9288759
references: Int J Oncol. 1998 Jul;13(1):5-9
references: 9625796
references: Genes Dev. 1998 Oct 1;12(19):2973-83
references: 9765199
references: Mol Cell. 1998 Sep;2(3):305-16
references: 9774969
references: Nature. 1998 Dec 17;396(6712):643-9
references: 9872311
references: Mol Cell Biol. 1999 Feb;19(2):1438-49
references: 9891077
references: Nature. 1999 Apr 22;398(6729):708-13
references: 10227293
references: Laryngoscope. 2004 Dec;114(12):2063-72
references: 15564824
references: Nature. 2000 Mar 2;404(6773):99-103
references: 10716451