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Cited by 245Cancer-related Molecular PathwaysVitamin D Research StudiesGenomics and Chromatin Dynamics

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

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Stambolsky, Perry, Tabach, Yuval, Fontemaggi, Giulia, Weisz, Lilach, Maor-Aloni, Revital, Sigfried, Zahava, Shiff, Idit, Kogan, Ira +6 more·2010·Cancer Cell
DOI 10.1016/j.ccr.2009.11.025PMC PMC2882298
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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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  • GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression.

    “In contrast to wt-p53, GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression [13,72,73,74,75,76,77].”

    From The p53 Pathway in Glioblastoma (2018) · cites this paper as [77]

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Authors
Stambolsky, P., Tabach, Y., Fontemaggi, G., Weisz, L., Maor-Aloni, R., Sigfried, Z., Shiff, I., Kogan, I., Shay, M., Kalo, E., Blandino, G., Simon, I., Oren, M., & Rotter, V.
Affiliations
  • Weizmann Institute of Science (IL)
  • Instituto Nazionale Tumori Regina Elena (IT)
  • Hebrew University of Jerusalem (IL)
Corresponding author
Stambolsky, Perry
ORCID
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2010-03
Volume
17
Issue
3
Pages
273-285
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccr.2009.11.025
PMC
PMC2882298
OpenAlex
W2073599728
Cited by
245
References
2
Citations by year
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FWCI
8.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R37CA040099)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
mutant p53, vitamin D receptor, vitamin D3, transcriptional regulation, gain-of-function p53, promoter binding, anti-apoptotic effects, tumor progression, gene expression modulation
MeSH terms
Cell Nucleus, Cholecalciferol, Humans, Promoter Regions, Genetic, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Apoptosis, Oligonucleotide Array Sequence Analysis, Vitamin D Response Element, Cell Line, Tumor, Chromatin Immunoprecipitation

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