摘要
由于组蛋白被修饰所引起的染色质结构的改变 ,在真核生物基因表达调控中发挥着重要的作用 ,这些修饰主要包括甲基化、乙酰化、磷酸化和泛素化等 ,其中组蛋白乙酰化尤为重要 .组蛋白乙酰转移酶 (HAT)和组蛋白去乙酰化酶 (HDAC)参与决定组蛋白乙酰化状态 .HAT通常作为多亚基辅激活物复合体的一部分 ,催化组蛋白乙酰化 ,导致染色质结构的松散、激活转录 ;而HDAC是多亚基辅抑制物复合体的一部分 ,使组蛋白去乙酰化 ,导致染色质集缩 ,并抑制基因的转录 .编码这些酶的基因染色体易位易于导致急性白血病的发生 .另一方面 ,已经确定了一些乙酰化修饰酶的基因在染色体上的位置 ,它们尤其倾向定位于染色体的断裂处 .综述了HAT和HDAC参与的组蛋白乙酰化与癌症发生之间关系的最新进展 ,以期进一步阐明组蛋白乙酰化修饰酶的生物学功能以及它们在癌症发生过程中的作用 .
Alterations in chromatin structure by histone post-translational modifications appear to play a central role in the regulation of gene transcription. Histone modifications consist of methylation, acetylation, phosphorylation and ubiquityination. Among them histone acetylation is of critical importance. The level of histone acetylation depends on the activity of two families of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs, which is frequently part of multisubunit coactivator complexes, lead to the relaxation of chromatin structure and transcriptional activation, while HDACs tend to associate with multisubunit corepressor complexes, resulting in chromatin condensation and transcriptional repression of specific target genes. Chromosomal translocations are often associated with acute leukemias, and a significant number of translocations involve genes encoding HATs and HDACs. On the other hand, some histone acetylation modifying enzymes have been located within chromosomal regions that are particularly prone to chromosomal breaks. The recent achievements in studies aimed at elucidating the biological roles of histone acetylation modifying enzymes and their potential impacts on the molecular changes involved in the development of cancers are reviewed.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2003年第1期19-23,共5页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金 ( 39970 384)
国家重点基础研究发展规划(G19990 5 390 2 )资助项目 .~~
