国家自然科学基金资助项目(30470720)和湖南省自然科学基金资助项目(06jj5058).
This work was supported by the grants from The National Natural Science Foundation of China (30470720) and The Natural Science Foundation of Hunan Province(06jj5058).
就三磷酸腺苷结合盒转运体A1(ABCA1)的结构、功能及调控研究的最新进展作一综述.ABCA1是一种膜整合蛋白,它具有多种复杂的功能,能介导细胞内磷脂和胆固醇流出到贫脂载脂蛋白A-Ⅰ,并且在高密度脂蛋白代谢过程中起重要作用.人类ABCA1变异将引起严重的高密度脂蛋白不足,其特征为载脂蛋白A-Ⅰ和高密度脂蛋白缺陷以及动脉粥样硬化.ABCA1的表达受到多种物质高度调控.细胞核受体主要通过作用于ABCA1启动子DR4元件参与调节ABCA1表达.第二信使环磷酸腺苷通过作用于转录水平和翻译水平上调ABCA1表达.细胞因子对ABCA1转录具有多效性和矛盾效应.除此以外,各种蛋白质和酶类如蛋白激酶A,蛋白激酶CK2,组织蛋白酶D也参与ABCA1表达调控.
ATP-binding cassette transporter A1(ABCA1) is a kind of membrane intergrate protein and may have multiple and diverse functions. It mediates the cellular efflux of phospholipids and cholesterol to lipid-poor apolipoproteinA-Ⅰ(apoA-Ⅰ) and plays a significant role in high density lipoprotein (HDL) metabolism. Mutations in human ABCA1 cause severe HDL deficiencies characterized by the virtual absence of apoA-Ⅰ and HDL and prevalent atherosclerosis. ABCA1 expression is highly regulated and implies a variety of molecular actors. All of the nuclear receptors which involve in regulation of ABCA1 expression act via the DR4 element in the ABCA1 promoter. cAMP up-regulates ABCA1 expression by acting both at the transcriptional and translational level. Cytokines have been shown to exert pleiotropic and antinomic effects on ABCA1 transcription. In addition to these, some of enzymes and proteins such as protein kinase A, protein kinase CK2, cathepsin D are involved in the regulation of ABCA1 expression. The recent progress in the structure, function and regulation of ABCA1 transporter is reviewed.
胡炎伟,唐朝克.三磷酸腺苷结合盒转运体A1研究的最新进展[J].生物化学与生物物理进展,2008,35(4):373-379
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