The Bmi-1 polycomb group gene in skin cancer: regulation of function by (-)-epigallocatechin-3-gallate.
The Bmi-1 polycomb group gene in skin cancer: regulation of function by (-)-epigallocatechin-3-gallate.
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皮肤癌中的 Bmi-1 多聚肌群基因：(-)-表没食子儿茶素-3-棓酸盐对功能的调节。
DOI：
10.1111/j.1753-4887.2008.00071.x
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发表时间：
2008-08
影响因子：
6.1
通讯作者：
Eckert RL
中科院分区：
文献类型：
--
作者：
Balasubramanian S;Lee K;Adhikary G;Gopalakrishnan R;Rorke EA;Eckert RL
PcG基因编码一类进化上保守的调节子，在果蝇中被发现为同源基因表达的抑制因子。在发育过程中，需要同源异型基因来建立身体分割模式。在哺乳动物系统中，PcG蛋白通过表观遗传机制(如染色质修饰)调节与发育和分化有关的基因。在细胞谱系确定过程中，它们作为基因表达的沉默因子密切相关，在促进细胞存活方面发挥着重要作用。由PcG基因编码的蛋白质由两个蛋白质复合体组成，它们协同作用调节基因的表达-Bmi-1复合体和Eed复合体。Bmi-1复合体包括Bmi-1、Mel-18、Mph1/Rae28、M33、Scmh1、Ring1a和Ring1b，而Eed复合体包括Eed、EzH1和EZH2。基因沉默的第一步是由Eed复合体介导的。含有EED的复合体通过募集组蛋白脱乙酰酶来修饰染色质，从而导致染色质的局部脱乙酰化。Eed复合体还催化组蛋白H3的Lys27的甲基化。在第二步中，Bmi-1复合体与组蛋白H3的甲基化Lys27结合，然后催化组蛋白H2A的泛素化。Eed和Bmi-1复合体之间的这种合作导致了基因表达的沉默。在这些事件完成后，Bmi-1复合体似乎仍然锚定在染色质上。Bmi-1PcG蛋白在基因沉默中具有特别重要的作用，因为它能够提高组蛋白泛素化的速度和程度。这是通过激活Ring 1B来实现的，Ring 1B是BMI-1复合体中存在的一种泛素连接酶(和PcG蛋白)。1，2Bmi-1在正常成人组织中也有功能。例如，老化的bmi-1−/−小鼠逐渐失去白血病、神经元和小脑颗粒细胞系3-5中的干细胞，而bmi-1缺陷的成纤维细胞表现出加速衰老和缓慢增殖率。6相反，BMI-1过表达促进细胞增殖。4 BMI-1在一些人类癌症中也过表达，包括结直肠癌、7和人类非小细胞肺癌。8此外，BMI-1过表达通过增加人类端粒酶逆转录酶水平和增加端粒酶活性的机制使人乳腺上皮细胞永生化。因此，BMI-1起着促进生存的调节作用。
The PcG genes encode a family of evolutionarily conserved regulators that were discovered in Drosophila as repressors of Homoeotic gene expression. Homeotic genes are required to establish body segmentation patterns during development. In mammalian systems, PcG proteins regulate genes involved in development and differentiation, via epigenetic (eg, chromatin modification) mechanisms. They are intimately involved as silencers of gene expression during cell lineage determination, and they play an important role in promoting cell survival. Proteins encoded by PcG genes comprise two protein complexes that act coordinately to regulate gene expression–the Bmi-1 complex and the Eed complex. The Bmi-1 complex includes Bmi-1, Mel-18, Mph1/Rae28, M33, Scmh1, Ring1A, and Ring1B, while the Eed complex includes Eed, EzH1, and EzH2. The first step in gene silencing is mediated by the Eed complex. Eed-containing complexes modify chromatin by recruiting histone deacetylase, which leads to local chromatin deacetylation. The Eed complex also catalyzes the methylation of Lys27 of histone H3. In the second step, the Bmi-1 complex binds to the methylated Lys27 of histone H3 and then catalyzes the ubiquitinylation of histone H2A. This cooperation between the Eed and Bmi-1 complexes leads to silencing of gene expression. The Bmi-1 complex appears to remain anchored to the chromatin after these events are completed. The Bmi-1 PcG protein has a particularly important role in gene silencing due to its ability to enhance the rate and extent of histone ubiquitinylation. This is accomplished through activation of Ring 1B, a ubiquitin ligase (and PcG protein) present in the Bmi-1 complex. 1, 2Bmi-1 also functions in normal adult tissues. For example, aging Bmi-1−/− mice progressively lose stem cells in the leukemic, neuronal, and cerebellar granule cell lineages3–5 and Bmi-1-deficient fibroblasts display enhanced senescence and slow proliferation rates. 6 In contrast, Bmi-1 overexpression enhances cell proliferation. 4 Bmi-1 is also overexpressed in some human cancers, including colorectal cancer, 7 and human nonsmall-cell lung cancer. 8 In addition, Bmi-1 overexpression immortalizes human mammary epithelial cells via a mechanism that involves increased levels of human telomerase reverse transcriptase and increased telomerase activity. 9 Thus, Bmi-1 functions as a pro-survival regulator.
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影响因子：
12.4
作者：
Denning, MF;Wang, Y;Qin, JZ
通讯作者：
Qin, JZ
影响因子：
8.8
作者：
Vonlanthen S;Heighway J;Altermatt HJ;Gugger M;Kappeler A;Borner MM;van Lohuizen M;Betticher DC
通讯作者：
Betticher DC
影响因子：
3.9
作者：
Ahmad, N;Gupta, S;Mukhtar, H
通讯作者：
Mukhtar, H
影响因子：
16
作者：
Cao, R;Tsukada, Y;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
1.7
作者：
Reinisch, Christina M.;Uthman, Aumaid;Pammer, Johannes
通讯作者：
Pammer, Johannes