Modulation of the Vitamin D3 Response by Cancer-Associated Mutant p53

Perry Stambolsky*, Yuval Tabach, Giulia Fontemaggi, Lilach Weisz, Revital Maor-Aloni, Zahava Sigfried, Idit Shiff, Ira Kogan, Moshe Shay, Eyal Kalo, Giovanni Blandino, Itamar Simon, Moshe Oren, Varda Rotter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

The p53 gene is mutated in many human tumors. Cells of such tumors often contain abundant mutant p53 (mutp53) protein, which may contribute actively to tumor progression via a gain-of-function mechanism. We applied ChIP-on-chip analysis and identified the vitamin D receptor (VDR) response element as overrepresented in promoter sequences bound by mutp53. We report that mutp53 can interact functionally and physically with VDR. Mutp53 is recruited to VDR-regulated genes and modulates their expression, augmenting the transactivation of some genes and relieving the repression of others. Furthermore, mutp53 increases the nuclear accumulation of VDR. Importantly, mutp53 converts vitamin D into an antiapoptotic agent. Thus, p53 status can determine the biological impact of vitamin D on tumor cells.

Original languageAmerican English
Pages (from-to)273-285
Number of pages13
JournalCancer Cell
Volume17
Issue number3
DOIs
StatePublished - 16 Mar 2010

Bibliographical note

Funding Information:
We wish to thank N. Goldfinger for assistance and R. Agami and C.C. Harris for plasmids. Supported by European Community FP6 funding (Contract 502983), Center of Excellence grant from the Flight Attendant Medical Research Institute, grant R37 CA40099 from the National Cancer Institute, the Dr. Miriam and Sheldon Adelson Medical Research Foundation, and the Yad Abraham Center for Cancer Diagnosis and Therapy. This publication reflects the authors' views and not necessarily those of the European Community.

Keywords

  • CELLCYCLE

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