Cellular senescence and tumor suppressor gene p16.
Cellular senescence and tumor suppressor gene p16.
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DOI：
10.1002/ijc.27316
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发表时间：
2012-04-15
影响因子：
6.4
通讯作者：
Srivatsan, Eri S.
中科院分区：
文献类型：
--
作者：
Rayess, Hani;Wang, Marilene B.;Srivatsan, Eri S.
细胞衰老是细胞生长的不可逆停滞。在细胞衰老期间发生生物化学和形态学变化，包括形成独特的细胞形态，例如扁平的细胞质。线粒体、内质网和溶酶体的功能受到影响，导致溶酶体和蛋白酶体途径受到抑制。细胞衰老可由许多因素触发，包括老化、DNA损伤、癌基因激活和氧化应激。虽然衰老的分子机制涉及p16和p53肿瘤抑制基因和端粒缩短，本文综述了p16控制的机制。p16介导的衰老通过视网膜母细胞瘤（Rb）途径起作用，抑制细胞周期蛋白依赖性激酶的作用，导致G1细胞周期停滞。Rb维持在低磷酸化状态，导致转录因子E2F1的抑制。p16表达的调控是复杂的，涉及表观遗传控制和多种转录因子。Pombe repressor complex 1（Pombe repressor complex 1）和Pombe repressor complex 2（PRC2）蛋白以及组蛋白去乙酰化酶在抑制p16表达的启动子高甲基化中起重要作用。虽然转录因子YY 1和Id 1抑制p16表达，但转录因子CTCF、Sp1和Ets家族成员激活p16转录。衰老发生与失活的抑制元件，导致p16的表达增强。
Cellular senescence is an irreversible arrest of cell growth. Biochemical and morphological changes occur during cellular senescence, including the formation of a unique cellular morphology such as flattened cytoplasm. Function of mitochondria, endoplasmic reticulum and lysosomes are affected resulting in the inhibition of lysosomal and proteosomal pathways. Cellular senescence can be triggered by a number of factors including, aging, DNA damage, oncogene activation and oxidative stress. While the molecular mechanism of senescence involves p16 and p53 tumor suppressor genes and telomere shortening, this review is focused on the mechanism of p16 control. The p16 mediated senescence acts through the retinoblastoma (Rb) pathway inhibiting the action of the cyclin dependant kinases leading to G1 cell cycle arrest. Rb is maintained in a hypophosphorylated state resulting in the inhibition of transcription factor E2F1. Regulation of p16 expression is complex and involves epigenetic control and multiple transcription factors. PRC1 (Pombe repressor complex 1) and PRC2 (Pombe repressor complex 2) proteins and histone deacetylases play an important role in the promoter hypermethylation for suppressing p16 expression. While transcription factors YY1 and Id1 suppress p16 expression, transcription factors CTCF, Sp1, and Ets family members activate p16 transcription. Senescence occurs with the inactivation of suppressor elements leading to the enhanced expression of p16.
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