Author/Authors :
Stambolsky، نويسنده , , Perry and Tabach، نويسنده , , Yuval and Fontemaggi، نويسنده , , Giulia and Weisz، نويسنده , , Lilach and Maor-Aloni، نويسنده , , Revital and Sigfried، نويسنده , , Zahava and Shiff، نويسنده , , Idit and Kogan، نويسنده , , Ira and Shay، نويسنده , , Moshe and Kalo، نويسنده , , Eyal and Blandino، نويسنده , , Giovanni and Simon، نويسنده , , Itamar and Oren، نويسنده , , Moshe and Rotter، نويسنده , , Varda، نويسنده ,
Abstract :
Summary
3 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.
