p53 Is Regulated by and Regulates Members of the γ-Secretase Complex
p53 Is Regulated by and Regulates Members of the γ-Secretase Complex
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DOI：
10.1159/000283483
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
da Costa, Cristine Alves
中科院分区：
文献类型：
--
作者：
Checler, Frederic;Dunys, Julie;da Costa, Cristine Alves
淀粉样β-肽是一组在阿尔茨海默病（AD）影响的大脑中积累的疏水肽的总称。这些淀粉样蛋白-β肽片段主要由称为γ-分泌酶复合物的酶机制产生，所述γ-分泌酶复合物由四种不同的蛋白质即早老素1（PS1）或PS2、nicastrin、Aph-1和Pen-2的缔合建立。AD的特征还在于似乎与肿瘤抑制因子p53相关的加剧的细胞死亡。有趣的是，γ-分泌酶复合物的所有成员都控制p53依赖性细胞死亡。另一方面，p53似乎能够直接或间接地调节PS1、PS2和Pen-2的表达和转录。这篇综述将集中在γ-分泌酶复合物和p53的成员之间的功能性串扰，并将讨论该癌基因在AD病理学中的假定意义。版权所有（C）2010 S. Karger AG，巴塞尔
Amyloid beta-peptides is the generic term for a set of hydrophobic peptides that accumulate in Alzheimer's disease (AD)-affected brains. These amyloid-beta peptide fragments are mainly generated by an enzymatic machinery referred to as gamma-secretase complex that is built up by the association of four distinct proteins, namely presenilin 1 (PS1) or PS2, nicastrin, Aph-1 and Pen-2. AD is also characterized by exacerbated cell death that appears linked to the tumor suppressor p53. Interestingly, all members of the gamma-secretase complex control p53-dependent cell death. On the other hand, p53 appears to be able to regulate directly or indirectly the expression and transcription of PS1, PS2 and Pen-2. This review will focus on the functional cross-talk between the members of the gamma-secretase complex and p53 and will discuss the putative implication of this oncogene in AD pathology. Copyright (C) 2010 S. Karger AG, Basel