Study On Alternative Splicing And Tissue-specificity Of Human ACAT2 Gene Expression As Well As Cloning And Analysis Of Monkey ACAT1 CDNA 5'-UTR

Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes the formation of cholesterol esters from long-chain fatty acyl coenzyme A and cholesterol. ACAT plays an important role in cellular cholesterol homeostasis. So far, in mammals, two ACAT genes have been identified. The ACAT1 that is found in almost all of the cells and tissues examined is believed to be crucial for maintaining cholesterol homeostasis while ACAT2 that is selectively expressed in liver and small intestine may be the major enzyme that 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. For these reasons, ACAT has been considered as one of major pharmaceutical targets for developing CE-lowering, anti-atherosclerosis and/or anti-AD drugs. In collaboration with professor Chang TY′s laboratory (Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA), our laboratory (State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China) has first reported the two human ACAT genomic DNAs, and investigated the expressional regulation of human ACAT1 gene. Based on the previous study, this work is mainly focused on the alternative splicing and tissue-specificity of human ACAT2 gene expression, and cloning and analysis of monkey ACAT1 cDNA 5′-UTR.Firstly, we studied the human ACAT2 mRNA variants from alternative splicing...