COREGULATION OF APP AND FERRITIN MRNAS AND APP FUNCTION

铁蛋白和APP基因的IL-1和铁共同调节应该会使 关于普遍存在的21号染色体的未探索的真正功能的光 APP蛋白是阿尔茨海默病的主要致病因素 疾病 APP生物学的两个特征应该阐明 这种丰富的膜蛋白。首先，APP基因，就像基因一样， 铁储存蛋白铁蛋白，在翻译过程中受到调节， IL-1和铁的水平（Rogers，1996年，已提交）。 的 APP-mRNA 5'非翻译区（5' UTR）与L和H- 铁蛋白mRNA 5 'UTR，包括铁蛋白mRNA和铁蛋白mRNA的保守位置。 反应元件（IRE）和强大的IL-1反应RNA序列。 铁释放铁蛋白mRNA从翻译抑制，通过去除 IRE结合蛋白（IRP，铁调节蛋白） 站点IRE。 APP中IRP和5 'UTR序列之间改变的相互作用- mRNA调节APP翻译响应IL-1信号和 细胞内铁水平。第二，初步证据表明， APP与星形细胞瘤胞浆内铁蛋白直接相互作用 细胞 我们将：1.探索“IRE样”RNA茎环的作用 在APP-mRNA起始密码子之前，与铁蛋白mRNA IRE一样， 与IRE结合蛋白（铁调节蛋白，IRP）相互作用。 2.检查L-或H-铁蛋白是否与APP蛋白相互作用 在星形胶质细胞和星形细胞瘤细胞中检测APP蛋白， 铁氧化酶活性

IL-1 and Iron co-regulation of the ferritin and APP genes should shed light on the unexplored true function of the ubiquitous chromosome 21 APP protein which is the main pathogenic contributor to Alzheimer's disease. Two features of APP biology should shed light on the role of this abundant membrane protein. First, the APP gene, like the gene for the iron storage protein ferritin, is regulated at the translational level in response to IL-1 and iron (Rogers, 1996, and Submitted). The APP-mRNA 5' untranslated region (5'UTR) is related to the L and H- ferritin mRNA 5'UTR, including a conserved placement of both Iron responsive elements (IREs) and powerful IL-1 responsive RNA sequences. Iron releases ferritin mRNAs from translational repression by removal of an IRE-binding protein (IRP, iron regulatory protein) from the 5' cap site IRE. Altered interaction between IRPs and 5'UTR sequences in APP- mRNA regulates APP translation in response IL-1 signals and intracellular iron levels. Second, preliminary evidence indicates that APP directly interacts with ferritin in the cytoplasm of astrocytoma cells. We will: 1. explore the action of an "IRE-like" RNA stem-loop in front of the APP-mRNA start codon which, like ferritin mRNA IREs, can interact with the IRE-binding proteins (Iron Regulatory Proteins, IRPs). 2. examine whether the L- or the H-ferritin interacts with APP protein in astrocytes and astrocytoma cells and examine APP protein for ferroxidase activity.