Deconstructing p53 transcriptional networks in tumor suppression.

Deconstructing p53 transcriptional networks in tumor suppression.
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解构肿瘤抑制中的p53转录网络。

DOI:
10.1016/j.tcb.2011.10.006
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发表时间:
2012-02
影响因子:
19
通讯作者:
Attardi, Laura D.
Attardi, Laura D.
中科院分区:
生物学1区
文献类型:
--
作者:
Bieging, Kathryn T.;Attardi, Laura D.

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P53是一种重要的肿瘤抑制因子,可在应激信号作用下诱导细胞凋亡、细胞周期停滞和衰老。虽然P53的转录激活对这些反应很重要,但肿瘤抑制的机制一直难以捉摸。到目前为止,还没有单一或复合敲除特定p53靶基因的小鼠重现p53缺失小鼠的显著肿瘤易感性。然而,最近对表达P53反式激活结构域突变的敲入小鼠的分析揭示了一组主要的新的直接P53靶基因,它们可能在体内介导肿瘤抑制。在这里,我们概述了众所周知的p53靶基因和同源基因敲除小鼠的肿瘤表型,然后介绍了最近发现的新的p53转录靶点,以及它们如何增强我们对p53转录网络的理解,这些网络对肿瘤抑制至关重要。
p53 is a pivotal tumor suppressor which induces apoptosis, cell-cycle arrest and senescence in response to stress signals. Although p53 transcriptional activation is important for these responses, the mechanisms underlying tumor suppression have been elusive. To date, no single or compound mouse knockout of specific p53 target genes has recapitulated the dramatic tumor predisposition that characterizes p53-null mice. Recently, however, analysis of knock-in mice expressing p53 transactivation domain mutants has revealed a group of primarily novel direct p53 target genes that may mediate tumor suppression in vivo. Here, we present an overview of well-known p53 target genes and the tumor phenotypes of the cognate knockout mice, then segue into the recent identification of new p53 transcriptional targets and how they enhance our understanding of p53 transcriptional networks central for tumor suppression.
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