The microtubule-associated tau protein has intrinsic acetyltransferase activity.
The microtubule-associated tau protein has intrinsic acetyltransferase activity.
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DOI：
10.1038/nsmb.2555
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发表时间：
2013-06
影响因子：
16.8
通讯作者：
Lee VM
中科院分区：
文献类型：
--
作者：
Cohen TJ;Friedmann D;Hwang AW;Marmorstein R;Lee VM
Tau蛋白是在包括阿尔茨海默病在内的一系列神经退行性Tau病中发现的神经原纤维缠结（nft）的构建块。最近，我们证明了tau蛋白被赖氨酸乙酰化广泛地翻译后修饰，这损害了tau蛋白的正常功能并促进了病理聚集。确定介导tau乙酰化的酶可以为未来的治疗提供靶点，旨在减少乙酰化tau的负担。在这里，我们报道哺乳动物tau蛋白具有能够催化自我乙酰化的内在酶活性。对tau乙酰转移酶活性的功能定位和生化分析表明，tau利用微管结合区域的催化半胱氨酸残基促进tau赖氨酸乙酰化，从而表明其机制与myst家族乙酰转移酶相似。鉴定tau是一种乙酰转移酶，为进一步了解tau的发病机制提供了一个框架，并突出了tau酶活性作为潜在的治疗靶点。
Tau proteins are the building blocks of neurofibrillary tangles (NFTs) found in a range of neurodegenerative tauopathies, including Alzheimer's disease. Recently, we demonstrated that tau is extensively post-translationally modified by lysine acetylation, which impairs normal tau function and promotes pathological aggregation. Identifying the enzymes that mediate tau acetylation could provide targets for future therapies aimed at reducing the burden of acetylated tau. Here, we report that mammalian tau proteins possess intrinsic enzymatic activity capable of catalyzing self-acetylation. Functional mapping of tau acetyltransferase activity followed by biochemical analysis revealed that tau uses catalytic cysteine residues in the microtubule-binding domain to facilitate tau lysine acetylation, thus suggesting a mechanism similar to that employed by MYST-family acetyltransferases. The identification of tau as an acetyltransferase provides a framework to further understand tau pathogenesis and highlights tau enzymatic activity as a potential therapeutic target.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.8
作者：
DREWES, G;TRINCZEK, B;MANDELKOW, E
通讯作者：
MANDELKOW, E
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
DOI：
10.1111/j.1749-6632.1996.tb34408.x
发表时间：
1996-01-01
期刊：
NEUROBIOLOGY OF ALZHEIMER'S DISEASE
影响因子：
--
作者：
Lee, VMY
通讯作者：
Lee, VMY
影响因子：
16.2
作者：
Min, Sang-Won;Cho, Seo-Hyun;Zhou, Yungui;Schroeder, Sebastian;Haroutunian, Vahram;Seeley, William W.;Huang, Eric J.;Shen, Yong;Masliah, Eliezer;Mukherjee, Chandrani;Meyers, David;Cole, Philip A.;Ott, Melanie;Gan, Li
通讯作者：
Gan, Li