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dc.contributor.authorZhao, Yingjunzh_CN
dc.contributor.authorWang, Yunshuzh_CN
dc.contributor.authorHu, Jinzh_CN
dc.contributor.authorZhang, Xianzh_CN
dc.contributor.authorZhang, Yun-Wuzh_CN
dc.contributor.author张弦zh_CN
dc.contributor.author张云武zh_CN
dc.date.accessioned2015-07-22T07:37:29Z
dc.date.available2015-07-22T07:37:29Z
dc.date.issued2012-03-30zh_CN
dc.identifier.citationJournal of Biological Chemistry, 2012,287(14):11141-11150zh_CN
dc.identifier.other20121514939792zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/93720
dc.description.abstractAccumulation of the neurotoxic 尾-amyloid (A尾) peptide in the brain is central to the pathogenesis of Alzheimer disease. A尾 is derived from the 尾-amyloid precursor protein (APP) through sequential cleavages by 尾- and 尾-secretases, and the production of A尾 is greatly affected by the subcellular localization of these factors. CUTA, the mammalian CutA divalent cation tolerance homolog (E. coli), has been proposed to mediate acetylcholinesterase activity and copper homeostasis, which are important in Alzheimer disease pathology. However, the exact function of CUTA remains largely unclear. Here we show that human CUTA has several variants that differ in their N-terminal length and are separated as heavy (H) and light (L) components. The H component has the longest N terminus and is membrane-associated, whereas the L component is N-terminally truncated at various sites and localized in the cytosol. Importantly, we demonstrate that the H component of CUTA interacts through its N terminus with the transmembrane domain of 尾-site APP cleaving enzyme 1 (BACE1), the putative 尾-secretase, mainly in the Golgi/trans-Golgi network. Overexpression and RNA interference knockdown of CUTA can reduce and increase BACE1-mediated APP processing/A尾 secretion, respectively. RNA interference of CUTA decelerates intracellular trafficking of BACE1 from the Golgi/trans-Golgi network to the cell surface and reduces the steady-state level of cell surface BACE1. Our results identify the H component of CUTA as a novel BACE1-interacting protein that mediates the intracellular trafficking of BACE1 and the processing of APP to A尾. 漏 2012 by The American Society for Biochemistry and Molecular Biology, Inc.zh_CN
dc.language.isoen_USzh_CN
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.zh_CN
dc.source.urihttp://dx.doi.org/10.1074/jbc.M111.330209zh_CN
dc.subjectActivation analysiszh_CN
dc.subjectCell membraneszh_CN
dc.subjectEscherichia colizh_CN
dc.subjectInterference suppressionzh_CN
dc.subjectMammalszh_CN
dc.subjectNeurodegenerative diseaseszh_CN
dc.subjectPhysiologyzh_CN
dc.subjectPositive ionszh_CN
dc.subjectRNAzh_CN
dc.titleCutA divalent cation tolerance homolog (Escherichia coli) (CUTA) regulates 尾-cleavage of 尾-amyloid precursor protein (APP) through interacting with 尾-site APP cleaving protein 1 (BACE1)zh_CN
dc.typeArticlezh_CN


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