在癌細胞中,，p53失活和端粒酶的重新激活是兩個最要的生物事件,。
研究發(fā)現(xiàn)，端粒酶催化亞基(TERT)的啟動子受到嚴謹調(diào)控,，并在體細胞中保持抑制狀態(tài),，以確保生命體有限的壽命，并抑制腫瘤的發(fā)生,。
最近,，美國堪薩斯大學醫(yī)學中心的研究人員發(fā)現(xiàn)，hTERT啟動子被p53,、p63及p73強烈的抑制,。
他們發(fā)現(xiàn)，在人類及老鼠細胞中,，p53介導的抑制作用是不同的,，它們分別是通過p53介導的c-Myc的轉(zhuǎn)錄抑制或者是通過E-box/E2F通路。
實驗發(fā)現(xiàn),，當p63TAα通過Sp1介導抑制時,，p63TAy也通過E2F信號介導了抑制作用的發(fā)生。
最后,，p73α及p73β通過NF-YB2也介導了對基因抑制作用,。
該研究表明了一個復雜的多因子機制，闡明了p53,、p63TAα,、p63TAy、 p73α及p73β通過不同的通路抑制端粒酶表達的機理,。相關(guān)論文發(fā)表在4月10日的The Journal of Biological Chemistry,。（生物谷Deepblue編譯）
doi: 10.1074/jbc.M111.319236
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Tumor suppressors p53, p63TAα, p63TAy, p73α and p73β use distinct pathways to repress telomerase expression
Yuan Yao, Marcia Bellon, Shary Shelton and Christophe Nicot.
The promoter of the telomerase catalytic subunit (TERT) is subject to tight regulation and remains repressed in somatic cells to ensure their limited life span and to prevent tumor initiation.Here we report that the hTERT promoter is strongly repressed by p53 and the related family members p63 and p73.We found that p53-mediated repression was different in human and mouse cells and occurred through p53-dependent transcription inhibition of c-Myc or through E-box/E2F pathways, respectively.While p63TAα-mediated repression occurred through Sp1, p63TAy-mediated repression occurred through E2F signaling.Finally, p73α and p73β-mediated repression occurred through NF-YB2.Our results show a complex multi-factorial mechanism used by p53 and its family members to keep hTERT expression under tight control.
