The discovery and role of CD147 as a subunit of gamma-secretase complex.
The discovery and role of CD147 as a subunit of gamma-secretase complex.
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DOI：
10.1358/dnp.2006.19.3.985932
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发表时间：
2006-04
影响因子：
--
通讯作者：
Shuxia Zhou;Hua Zhou;P. Walian;B. Jap
中科院分区：
文献类型：
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作者：
Shuxia Zhou;Hua Zhou;P. Walian;B. Jap
γ -分泌酶是一种具有异常天冬氨酸蛋白酶活性的膜蛋白复合物，可在其跨膜区域内切割多种I型跨膜蛋白，如APP、Notch和E-cadherin。γ -分泌酶最初被发现是因为它在阿尔茨海默病中致病的β肽的产生中起作用。大量证据表明，早老素、nicastrin、APH-1和PEN-2这四种成分对γ -分泌酶活性是必要和充分的。然而，根据对过表达这四种成分的细胞进行的研究结果，伽马分泌酶复合物的调节成分的存在已经被假设。最近，通过从HeLa细胞膜中纯化和表征内源性复合物，发现了γ -分泌酶复合物的另一个亚基——膜蛋白CD147。从γ -分泌酶复合物中去除CD147会增加β肽的产生。阐明CD147影响γ -分泌酶复合物活性的分子机制将有助于我们进一步了解阿尔茨海默病的发病机制，并可能开发新的治疗方法。
Gamma-secretase is a membrane protein complex with unusual aspartyl protease activity that cleaves a variety of type I transmembrane proteins, such as APP, Notch and E-cadherin, within their transmembranous regions. Gamma-secretase was first recognized because of its role in the production of Abeta peptides that are pathogenic in Alzheimer's disease. There is overwhelming evidence demonstrating that four components, presenilin, nicastrin, APH-1 and PEN-2, are necessary and sufficient for gamma-secretase activity. However, based on the findings of studies conducted on cells overexpressing these four components, the existence of regulatory components of the gamma-secretase complex has been postulated. Recently, an additional subunit of the gamma-secretase complex, membrane protein CD147, has been identified through the purification and characterization of endogenous complexes from HeLa cell membranes. Removal of CD147 from gamma-secretase complexes increases the production of Abeta-peptides. Elucidating the molecular mechanism by which CD147 exerts its effect on the activity of the gamma-secretase complex will help us to further understand the pathogenesis of Alzheimer's disease, and may allow for the development of novel therapeutics.