Brown M S, Goldstein J L
Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
Nutr Rev. 1998 Feb;56(2 Pt 2):S1-3; discussion S54-75. doi: 10.1111/j.1753-4887.1998.tb01680.x.
Mammalian cells use an exquisitely sensitive mechanism to control the amount of cholesterol and fatty acids in their membranes. This process relies on a feedback system that adjusts the rates of transcription of genes encoding the low density lipoprotein receptor and multiple enzymes in the cholesterol and fatty acid biosynthetic pathways. When cellular cholesterol levels are depleted, these genes are all transcribed in abundant amounts, and their transcription is repressed when sterols build up within the cell. Until recently, the mechanism of this regulation was elusive. How do cells sense the level of a membrane-embedded lipid such as cholesterol and how is this information transmitted to the nucleus where gene transcription is regulated? Answers are now beginning to emerge from the study of a newly discovered family of transcription-regulating proteins called sterol regulatory element binding proteins.
哺乳动物细胞利用一种极其敏感的机制来控制其细胞膜中胆固醇和脂肪酸的含量。这一过程依赖于一个反馈系统,该系统会调整编码低密度脂蛋白受体以及胆固醇和脂肪酸生物合成途径中多种酶的基因的转录速率。当细胞内胆固醇水平降低时,这些基因都会大量转录,而当细胞内固醇积累时,它们的转录就会受到抑制。直到最近,这种调节机制仍不清楚。细胞是如何感知像胆固醇这样嵌入细胞膜的脂质水平的,以及这些信息是如何传递到调节基因转录的细胞核中的?现在,对一类新发现的称为固醇调节元件结合蛋白的转录调节蛋白家族的研究开始给出答案。