BACE1 Gene Expression and Protein Degradation
BACE1 Gene Expression and Protein Degradation
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DOI：
10.1196/annals.1332.004
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发表时间：
2004-12
影响因子：
5.2
通讯作者：
Weihui Zhou;H. Qing;Yigang Tong;Weihong Song
中科院分区：
文献类型：
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作者：
Weihui Zhou;H. Qing;Yigang Tong;Weihong Song
摘要：淀粉样蛋白β在脑内沉积是阿尔茨海默病的主要病理特征。淀粉样蛋白β是由β-淀粉样前体蛋白通过β分泌酶和γ分泌酶产生的。BACE1对淀粉样前体蛋白β位点的蛋白降解作用是产生淀粉样蛋白β所必需的。BACE1是参与裂解淀粉样前体蛋白的主要β分泌酶，已被鉴定为1型膜相关天冬氨酸蛋白酶。在本研究中，我们发现BACE1基因的表达受TATA缺失启动子的控制。BACE1基因的表达在转录水平上受到严格调控，转录因子Sp1在BACE1加工淀粉样前体蛋白产生淀粉样蛋白β中起重要作用。此外，我们发现BACE1蛋白是泛素化的，BACE1蛋白的降解和淀粉样前体蛋白的加工受泛素-蛋白酶体途径的调控。
Abstract: Deposition of amyloid β protein in the brain is the major pathological feature of Alzheimer's disease. Amyloid β protein is generated from β‐amyloid precursor protein by β‐secretase and γ‐secretase. Proteolytic processing of amyloid precursor protein at the β site by BACE1 is essential to generate amyloid β protein. BACE1, the major β‐secretase involved in cleaving amyloid precursor protein, has been identified as a type 1 membrane‐associated aspartyl protease. In this study, we found that BACE1 gene expression is controlled by a TATA‐less promoter. BACE1 gene expression is tightly regulated at the transcriptional level and the transcription factor Sp1 plays an important role in regulation of BACE1 to process amyloid precursor protein generating amyloid β protein. Furthermore, we found that BACE1 protein is ubiquitinated, and the degradation of BACE1 proteins and amyloid precursor protein processing are regulated by the ubiquitin‐proteasome pathway.