p53: guardian of ploidy.

p53: guardian of ploidy.
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DOI:
10.1016/j.molonc.2011.07.007
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发表时间:
2011-08
期刊:
影响因子:
6.6
通讯作者:
Oren M
Oren M
中科院分区:
医学2区
文献类型:
--
作者:
Aylon Y;Oren M

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非整倍体,通常在四倍体之前,是实体瘤的标志之一。事实上,非整倍体和四倍体都是足以驱动肿瘤转化和癌症进展的致癌发生。真正的形式,肿瘤抑制基因p53阻碍传播这些危险的染色体事件,无论是煽动不可逆的细胞周期停滞或凋亡。肿瘤抑制因子Lats 2与其他肿瘤抑制蛋白如BRCA 1/2和BubR 1一起,沿着是四倍体细胞p53依赖性消除的中心。毫不奇怪,这些蛋白质在肿瘤中经常失活或下调,与p53失活协同作用,以建立对非二倍体状态的“耐受”气氛。
Aneuploidy, often preceded by tetraploidy, is one of the hallmarks of solid tumors. Indeed, both aneuploidy and tetraploidy are oncogenic occurrences that are sufficient to drive neoplastic transformation and cancer progression. True to form, the tumor suppressor p53 obstructs propagation of these dangerous chromosomal events by either instigating irreversible cell cycle arrest or apoptosis. The tumor suppressor Lats2, along with other tumor inhibitory proteins such as BRCA1/2 and BubR1, are central to p53-dependent elimination of tetraploid cells. Not surprisingly, these proteins are frequently inactivated or downregulated in tumors, synergizing with p53 inactivation to establish an atmosphere of “tolerance” for a nondiploid state.
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