PURIFICATION OF NOVEL FACTOR INVOLVED IN PRODUCTION OF APO B48

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It is now well established that increased plasma cholesterol levels are associated with an increased risk in heart disease. The main carrier of cholesterol in the bloodstream is a protein called apo-B. Because apo-B has such an important physiological role, our laboratory is studying how this protein is produced. There are two forms of apo-B in the plasma a large form, apo-B100, and a small form, apo-B48, which is about half the size of apo-B100. Apo-B48 is important in the absorption and transport of dietary cholesterol. We have found that there is an unusual mechanism responsible for the production of this short form of the apo-B protein. Our research has been investigating this mechanism at the biochemical and molecular level. We have found that one of the factors involved in this pathway is expressed at high levels in baboon kidney. Therefore, we are trying to purify this factor from baboon kidney in order to identify it and understand its role in the synthesis of apo-B4 8. The results from our research will provide insight into how the body handles dietary cholesterol. Our long-term goal is to use this information to design therapies that may help lower blood cholesterol levels and prevent the development of atherosclerosis in the future. FUNDING NIH grants HL45478 and RR00166. Mehta, A. and D.M. Driscoll. A sequence-specific RNA-binding protein complements apobec-1 to edit apolipoprotein-B mRNA. Mol. Cell. Biol., 18 4426-4432, 1998