INTERMEDIARY METABOLISM AND A NOVEL RNA BINDING PROTEIN

脂肪酸合成酶是一种对从头合成脂肪酸起关键作用的酶 综合。葡萄糖通过介导Fas基因表达调控人Fas基因表达 稳定性。葡萄糖还诱导178 kD的蛋白质与 Fas信息，表明该蛋白与中间代谢有关 和脂肪酸的生物合成。该RNA结合蛋白已被纯化 并进行了部分测序。它的主要结合元素已经确定。 本应用程序中的研究将检验这一假设 葡萄糖诱导蛋白通过以下途径调节从头合成脂肪酸 介导Fas基因的表达。具体目标是：1-克隆和 表达178kD的Fas mRNA结合蛋白。2-确定绑定 小鼠不同成脂组织中178kD蛋白活性的研究 建立小鼠实验性糖尿病模型。3-展示 178kD结合元件参与信息稳定性。4-至 在HepG2细胞中灭活178kD蛋白并测定对其的影响 脂蛋白分泌和细胞生长。5-过度表达178 kD 蛋白在HepG2细胞中的表达及其对脂蛋白分泌的影响 和细胞生长。 我们已经鉴定出一种新的RNA结合蛋白。 鉴定这种RNA结合蛋白可以为 针对与异常相关的人类疾病的创新疗法 脂肪酸和葡萄糖代谢。这些疾病包括肥胖， 高脂血症、非胰岛素依赖型糖尿病甚至 恶性肿瘤。

Fatty acid synthase (FAS) is an enzyme critical for de novo fatty acid synthesis. Glucose regulates human FAS expression by mediating FAS mRNA stability. Glucose also induces the binding of a 178 kD protein to the FAS message, suggesting that this protein links intermediary metabolism and fatty acid biosynthesis. This RNA binding protein has been purified and partially sequenced. Its major binding element has been identified. The studies in this application will test the hypothesis that this glucose-inducible protein regulates de novo fatty acid synthesis by mediating FAS gene expression. The specific aims are: 1-To clone and express the 178 kD FAS mRNA binding protein. 2-To determine the binding activity of the 178 kD protein in different lipogenic tissues in the setting of experimental diabetes in mice. 3-To demonstrate the involvement of the 178 kD binding element in message stability. 4-To inactivate the 178 kD protein in HepG2 cells and determine effects on lipoprotein secretion and cell growth. 5-To overexpress the 178 kD protein in HepG2 cells and determine effects on lipoprotein secretion and cell growth. We have identified what appears to be a novel RNA binding protein. Characterizing this RNA binding protein could provide the basis for innovative therapies aimed at human disorders associated with abnormal fatty acid and glucose metabolism. These disorders include obesity, hyperlipidemia, non-insulin-dependent diabetes mellitus and even malignancies.