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本文引用的文献

1
Accumulation of multiacetylated forms of histones by trichostatin A and its developmental consequences in early starfish embryos.曲古抑菌素A诱导的组蛋白多乙酰化形式的积累及其对海星早期胚胎发育的影响
Rouxs Arch Dev Biol. 1993 Feb;202(3):144-151. doi: 10.1007/BF00365304.
2
Clinical development of histone deacetylase inhibitors as anticancer agents.组蛋白去乙酰化酶抑制剂作为抗癌药物的临床开发。
Annu Rev Pharmacol Toxicol. 2005;45:495-528. doi: 10.1146/annurev.pharmtox.45.120403.095825.
3
Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors.Ku70乙酰化介导组蛋白去乙酰化酶抑制剂诱导的神经母细胞瘤细胞死亡。
Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4842-7. doi: 10.1073/pnas.0408351102. Epub 2005 Mar 18.
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Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer.组蛋白H4赖氨酸16位乙酰化缺失和赖氨酸20位三甲基化是人类癌症的常见特征。
Nat Genet. 2005 Apr;37(4):391-400. doi: 10.1038/ng1531. Epub 2005 Mar 13.
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Histone variants: deviants?组蛋白变体:异类?
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6
Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway.组蛋白去乙酰化酶抑制剂通过激活死亡受体途径诱导肿瘤选择性凋亡。
Nat Med. 2005 Jan;11(1):71-6. doi: 10.1038/nm1160. Epub 2004 Dec 26.
7
Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells.组蛋白去乙酰化酶抑制剂的肿瘤选择性作用涉及急性髓系白血病细胞中TRAIL的诱导。
Nat Med. 2005 Jan;11(1):77-84. doi: 10.1038/nm1161. Epub 2004 Dec 26.
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Histone deacetylase inhibitors.组蛋白去乙酰化酶抑制剂
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Histone deacetylase inhibitors open new doors in cancer therapy.
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Topoisomerase II and histone deacetylase inhibitors delay the G2/M transition by triggering the p38 MAPK checkpoint pathway.拓扑异构酶II和组蛋白脱乙酰酶抑制剂通过触发p38丝裂原活化蛋白激酶(MAPK)检查点途径来延迟G2/M期转换。
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组蛋白去乙酰化酶抑制剂对异染色质的影响:对癌症治疗有何启示?

The effects of histone deacetylase inhibitors on heterochromatin: implications for anticancer therapy?

作者信息

Taddei Angela, Roche Danièle, Bickmore Wendy A, Almouzni Geneviève

机构信息

Institut Curie, Research Section, UMR 218 du CNRS, 26 Rue d'Ulm, 75248 Paris cedex 05, France.

出版信息

EMBO Rep. 2005 Jun;6(6):520-4. doi: 10.1038/sj.embor.7400441.

DOI:10.1038/sj.embor.7400441
PMID:15940285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1369099/
Abstract

Histone acetylation regulates many chromosome functions, such as gene expression and chromosome segregation. Histone deacetylase inhibitors (HDACIs) induce growth arrest, differentiation and apoptosis of cancer cells ex vivo, as well as in vivo in tumour-bearing animal models, and are now undergoing clinical trials as anti-tumour agents. However, little attention has been paid to how HDACIs function in these biological settings and why different cells respond in different ways. Here, we discuss the consequences of inhibiting histone deacetylases in cycling versus non-cycling cells, in light of the dynamics of histone acetylation patterns with a specific emphasis on heterochromatic regions of the genome.

摘要

组蛋白乙酰化调节许多染色体功能,如基因表达和染色体分离。组蛋白去乙酰化酶抑制剂(HDACIs)在体外以及在荷瘤动物模型体内均可诱导癌细胞的生长停滞、分化和凋亡,目前正作为抗肿瘤药物进行临床试验。然而,对于HDACIs在这些生物学环境中的作用方式以及不同细胞为何有不同反应,人们关注较少。在此,我们根据组蛋白乙酰化模式的动态变化,特别是着重于基因组的异染色质区域,来讨论在循环细胞与非循环细胞中抑制组蛋白去乙酰化酶的后果。