alexa Modulation of the vitamin D3 response by cancer-associated mutant p53.
Oncology

Oncology

Chemotherapy: Open Access

Author(s): Stambolsky P, Tabach Y, Fontemaggi G, Weisz L, MaorAloni R

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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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This article was published in Cancer Cell. and referenced in Chemotherapy: Open Access

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