在癌細(xì)胞中,，p53失活和端粒酶的重新激活是兩個(gè)最要的生物事件。
研究發(fā)現(xiàn),，端粒酶催化亞基(TERT)的啟動(dòng)子受到嚴(yán)謹(jǐn)調(diào)控,，并在體細(xì)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(guó)堪薩斯大學(xué)醫(yī)學(xué)中心的研究人員發(fā)現(xiàn),，hTERT啟動(dòng)子被p53,、p63及p73強(qiáng)烈的抑制。
他們發(fā)現(xiàn),，在人類(lèi)及老鼠細(xì)胞中,，p53介導(dǎo)的抑制作用是不同的，它們分別是通過(guò)p53介導(dǎo)的c-Myc的轉(zhuǎn)錄抑制或者是通過(guò)E-box/E2F通路,。
實(shí)驗(yàn)發(fā)現(xiàn),，當(dāng)p63TAα通過(guò)Sp1介導(dǎo)抑制時(shí),，p63TAy也通過(guò)E2F信號(hào)介導(dǎo)了抑制作用的發(fā)生。
最后,，p73α及p73β通過(guò)NF-YB2也介導(dǎo)了對(duì)基因抑制作用,。
該研究表明了一個(gè)復(fù)雜的多因子機(jī)制，闡明了p53,、p63TAα,、p63TAy、 p73α及p73β通過(guò)不同的通路抑制端粒酶表達(dá)的機(jī)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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PMID:
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.
