I2（PP2A）/SET 抑制 PP2A 活性和 tau 异常过度磷酸化的机制。
Mechanism of inhibition of PP2A activity and abnormal hyperphosphorylation of tau by I2(PP2A)/SET.
机构信息
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
出版信息
FEBS Lett. 2011 Sep 2;585(17):2653-9. doi: 10.1016/j.febslet.2011.07.020. Epub 2011 Jul 28.
Abstract
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(2)(PP2A) 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.
摘要
蛋白磷酸酶-2A（PP2A）活性在阿尔茨海默病大脑中受损，受两种内源性抑制剂调节，其中之一是 I（2）（PP2A），一种 277 个氨基酸长的蛋白质，也称为 SET。在这里，我们报告说，I（2）（PP2A）的氨基末端片段（I（2NTF）；aa 1-175）和羧基末端片段（I（2CTF）；aa 176-277）通过与其催化亚基 PP2Ac 结合来抑制 PP2A，并导致 tau 的过度磷酸化。I（2CTF）中的 C 末端酸性区域和 I（2NTF）中的 Val 92 对于它们与 PP2Ac 的结合和抑制磷酸酶活性是必需的。
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