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

doi:10.1016/j.ccr.2009.11.025

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

Department of Microbiology and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

213 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 language	English
Pages (from-to)	273-285
Number of pages	13
Journal	Cancer Cell
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2009.11.025
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2009.11.025

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title = "Modulation of the Vitamin D3 Response by Cancer-Associated Mutant p53",

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.",

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AU - Maor-Aloni, Revital

AU - Sigfried, Zahava

AU - Shiff, Idit

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AU - Shay, Moshe

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AU - Blandino, Giovanni

AU - Simon, Itamar

AU - Oren, Moshe

AU - Rotter, Varda

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

Abstract

Bibliographical note

Keywords

UN SDGs

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