Nuclear Matrix Protein SMAR1 Represses c-Fos-mediated HPV18 E6 Transcription through Alteration of Chromatin Histone Deacetylation

摘要: Matrix attachment region (MAR)-binding proteins have been implicated in the transcriptional regulation of host as well viral genes, but their precise role HPV-infected cervical cancer remains unclear. Here we show that HPV18 promoter contains consensus MAR element LCR and E6 sequences where SMAR1 binds reinforces silencing. In fact, curcumin-induced up-regulation ensures recruitment SMAR1-HDAC1 repressor complex at sequences, thereby decreasing histone acetylation H3K9 H3K18, leading to reorientation chromatin. As a consequence, c-Fos binding putative AP-1 sites on is inhibited. depletion interrupts degradation E6-mediated p53 lysine acetyl transferase, Tip60. Tip60, turn, acetylates p53, restoring p53-mediated transactivation proapoptotic genes ensure apoptosis. This hitherto unexplained function signifies potential this unique scaffold matrix-associated region-binding protein critical regulator anti-apoptotic network HPV18-infected adenocarcinoma. These results also justify candidature curcumin for treatment carcinoma.