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- W2004638862 abstract "ackground. Expression of the p53-paralog DNp73 oncoene increases progressively in chronic hepatitis, cirrhosis nd HCC and greatly contributes to the chemoresistant henotype of HCC cells. DNp73 isoforms do not activate ranscription and do not induce apoptosis but act as domiant negative inhibitors of both p53 and TAp73. DNp73s are xpressed from the intragenic P2p73 promoter and we have ecently shown that its activity is positively regulated in heptocytes by beta-catenin and p65/NFkB. In silico analisys of he P2p73 promoter indicates that it contains two conserved SRE elements. im. To characterize the effects of -interferon on DNp73 xpression and to evaluate the functional consequences on ell proliferation and viability. ethods. Chromatin was immunoprecipatated from ntreated and IFN treated Huh7 cells with anti-AcH3, nti-STAT2, anti-P-STAT2, anti-HDAC1, anti-p300, antiY1 and anti-Pol II antibodies. DNp73 mRNA levels were uantitated real-time PCR. esults. ChIP analysis showed that both ISRE sites are ound in vivo by Stat2 and by its phosphorilated form after h of IFN treatment. Endogenous DNp73 mRNA levels re downregulated by IFN . Immunoblot analysis showed a trong DNp73 protein downregulation after IFN-treatment. hIP analysis showed that, before the IFN treatment, H3 ysines are acetylated and p300 and Pol II are bound to the 2p73 promoter, mirroring active transcription, whereas after h treatment (when the ISGF3 complex is recruited), Pol II nd p300 binding is lost whereas HDAC1, a well-known trancription cofactor related to transcriptional repression, and he YY1 co-repressor are actively recruited. These results ndicate that the recruitment of the ISGF3 complex to the 2p73promoter has a repressive activity and suggest that this h o a a isease 41 (2009) A1–A19" @default.
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- W2004638862 date "2009-04-01" @default.
- W2004638862 modified "2023-09-26" @default.
- W2004638862 title "545 THE P53-PARALOG DNP73 ONCOGENE IS REPRESSED BY α-IFN/STAT2 THROUGH THE RECRUITMENT OF YY1 AND HDAC1 TRANSCRIPTIONAL REPRESSORS" @default.
- W2004638862 doi "https://doi.org/10.1016/s0168-8278(09)60547-x" @default.
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