Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin
Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin
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DOI：
10.1093/hmg/10.7.693
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发表时间：
2001-04-01
影响因子：
3.5
通讯作者：
Wade, PA
中科院分区：
文献类型：
--
作者：
Wade, PA
癌细胞表现出一系列独特的特性，使其与正常细胞相区别。这些特征包括生长速率增加、分化丧失、逃避细胞死亡途径、逃避抗增殖信号、减少对外源性生长因子的依赖以及逃避复制性衰老。恶性细胞获得这些特征需要损害正常的细胞控制机制。在过去的几年里，越来越明显的是，癌细胞中常见的分子变化的一个重要子集涉及基因表达的不适当调节。这篇综述将讨论其破坏有助于恶性表型的调节途径，由于Rb蛋白家族的破坏而导致的I类组蛋白脱乙酰酶HDAC 1和HDAC 2的脱乙酰化失败并因此抑制转录已被牢固地确立为导致生长速率和细胞增殖增加的机制，最近的数据表明，该调节回路还执行G，DNA损伤、细胞衰老和接触抑制下游的检查点阻滞。与这种去乙酰化失败相反，现在似乎可能的是，分化状态的变化可能部分地由II类组蛋白去乙酰化酶介导的不适当的去乙酰化和伴随的转录抑制引起。HDAC 4、HDACS和HDAC 6的这种不适当的去乙酰化是在它们从细胞质重新定位到细胞核之后发生的。因此，癌细胞的多种经典特征可以通过不适当的组蛋白脱乙酰化来表现。
Cancer cells exhibit a set of unique properties that distinguish them from their normal counterparts, Among these features are increased growth rates, loss of differentiation, escape from cell death pathways, evasion of anti-proliferative signals, a decreased reliance on exogenous growth factors and escape from replicative senescence. Acquisition of these features by malignant cells requires impairment of normal cellular control mechanisms. Over the past few years, it has become increasingly apparent that an important subset of the molecular changes commonly found in cancer cells involves inappropriate regulation of gene expression. This review will address regulatory pathways whose disruption contributes to the malignant phenotype, The failure to deacetylate and thus repress transcription by the Class I histone deacetylases HDAC1 and HDAC2 due to disruption of the Rb family of proteins has been firmly established as a mechanism leading to increases in growth rate and cellular proliferation, Recent data suggest that this regulatory circuit also executes G, checkpoint arrest downstream of DNA damage, cellular senescence and contact inhibition. In contrast to this failure to deacetylate, it now seems probable that changes in differentiation status may result in part from inappropriate deacetylation and concomitant transcriptional repression mediated by the Class II histone deacetylases, This inappropriate deacetylation by HDAC4, HDACS and HDAC6 follows their relocalization from the cytoplasm to the nucleus. Thus, multiple classical features of cancer cells can be manifested by improper histone deacetylation.