Study On Molecular Mechanism For The Specific Expression Of ACAT2 Gene And Cloning Of Mouse ACAT1 CDNA 5'-UTR

Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme present in various eukaryotic cells and catalyzes the formation of cholesterol esters (CE) from long-chain fatty acyl coenzyme A and cholesterol. Up to now, two ACAT genes have been identified in mammals (ACAT1 and ACAT2). In adult human tissues, ACAT1 protein is found in almost all of the cells and tissues examined, and believed to be crucial for maintaining cholesterol homeostasis. On the other hand, ACAT2 is selectively expressed in liver and small intestine, mainly involved in the dietary cholesterol absorption and assembly of apoB-containing lipoprotein. ACATs also play important roles in some serious human diseases including atherosclerosis, Alzheimer's disease (AD) and gallstone. Therefor, ACAT has attracted much attention of researchers to screen effective drugs for being considered as one important pharmaceutical target.So far, the natural ACAT enzyme has never been purified to homogeneity because of its very low content as an integral membrane protein present in the endoplasmic reticulum. So cloning of its gene has provided a necessary and effective tool to research the enzyme in gene levels. In 1993, professor TY Chang's group in Dartmouth Medical School (USA) first succeeded in cloning a human ACAT gene, now known as ACAT1 cDNA K1. Professor Bo-Liang Li's Laboratory (I finished my degree thesis in this Lab.) of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, the collaboration group of professor TY Chang's Laboratory, first reported the human ACAT1 and ACAT2 genomic DNAs, cloned their promoter and investigated the expressional regulation of human ACAT1 gene.