组蛋白
组蛋白脱乙酰基酶
组蛋白乙酰转移酶
癌症研究
生物
髓系白血病
HDAC1型
染色质
乙酰化
表观遗传学
细胞生物学
HDAC11型
心理压抑
染色质重塑
转录调控
基因
遗传学
基因表达
作者
Gerd H Moe-Behrens,Pier Paolo Pandolfi
出处
期刊:PubMed
日期:2003-06-01
卷期号:7 (2): 139-59
被引量:25
摘要
Histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities determine the acetylation status of histones, and have the ability to regulate gene expression through chromatin remodeling. Aberrant histone acetylation is known to play a key role in leukemogenesis. A common biologic feature, shared by genetically heterogeneous acute myeloid leukemias (AML), is a block of hematopoietic differentiation by the fusion proteins produced by chromosomal translocations. In many cases, a DNA binding fusion protein, which abnormally interacts with transcriptional co-regulators and increases local concentration of HDAC complexes, imposes a transcriptional repressive state on target gene promoters, which may become refractory to physiologic stimuli. To target this transcriptional repression, HDAC inhibitors (HDACI) have been developed, which are thought to derepress a set of genes whose transcriptional activation induces cell-cycle arrest, apoptosis and cellular differentiation and thus anti-tumoral activity. Therefore, HDACI might be utilized as effective antileukemic agents, and are currently under clinical trials.
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