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JBC:揭示抑癌基因抑制端粒酶表达的机制

2012/4/14 作者:Deepblue   来源:生物谷 我要评论0
Tags:   肿瘤  癌症    

在癌细胞中,p53失活和端粒酶的重新激活是两个最要的生物事件。

研究发现,端粒酶催化亚基(TERT)的启动子受到严谨调控,并在体细胞中保持抑制状态,以确保生命体有限的寿命,并抑制肿瘤的发生。

最近,美国堪萨斯大学医学中心的研究人员发现,hTERT启动子被p53、p63及p73强烈的抑制。

他们发现,在人类及老鼠细胞中,p53介导的抑制作用是不同的,它们分别是通过p53介导的c-Myc的转录抑制或者是通过E-box/E2F通路。

实验发现,当p63TAα通过Sp1介导抑制时,p63TAy也通过E2F信号介导了抑制作用的发生。

最后,p73α及p73β通过NF-YB2也介导了对基因抑制作用。

该研究表明了一个复杂的多因子机制,阐明了p53、p63TAα、p63TAy、 p73α及p73β通过不同的通路抑制端粒酶表达的机理。相关论文发表在4月10日的The Journal of Biological Chemistry。(生物谷Deepblue编译)

doi: 10.1074/jbc.M111.319236
PMC:
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.



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