Mechanism of inhibition of PP2A activity and abnormal hyperphosphorylation of tau by I2PP2A/SET

被引：96

作者：

Arnaud, Lisette ^{[1
]}

Chen, She ^{[1
]}

Liu, Fei ^{[1
]}

Li, Bin ^{[1
]}

Khatoon, Sabiha ^{[1
]}

Grundke-Iqbal, Inge ^{[1
]}

Iqbal, Khalid ^{[1
]}

机构：

[1] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA

来源：

FEBS LETTERS | 2011年 / 585卷 / 17期

基金：

美国国家卫生研究院;

关键词：

Alzheimer disease; Asparaginyl endopeptidase; Ischemic stroke; PHAPII; Protein phosphatase-2A; Tauopathies; PROTEIN PHOSPHATASE 2A; ACTIVATING FACTOR-I; SET; DISEASE; IDENTIFICATION; LOCALIZATION; DEPHOSPHORYLATION; PHOSPHORYLATION; PURIFICATION; EXPRESSION;

D O I：

10.1016/j.febslet.2011.07.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein phosphatase-2A (PP2A) activity, which is compromised in Alzheimer disease brain, is regulated by two endogenous inhibitors, one of them being I-2(PP2A), a 277 amino acid long protein also known as SET. Here we report that both the amino terminal fragment (I-2NTF; aa 1-175) and the carboxy terminal fragment (I-2CTF; aa 176-277) of I-2PP2A inhibit PP2A by binding to its catalytic subunit PP2Ac and cause hyperphosphorylation of tau. The C-terminal acidic region in I-2CTF and Val 92 in I-2NTF are essential for their association with PP2Ac and inhibition of the phosphatase activity. Structured summary of protein interactions: I2PP2A physically interacts with PP2A-C by anti tag coimmunoprecipitation (view interaction 1, 2) I2PP2A physically interacts with PP2A-C by pull down (view interaction 1, 2) PP2A-A physically interacts with PP2A-B and PP2A-C by pull down (view interaction) (C) 2011 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：2653 / 2659

页数：7

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