A769662, a novel activator of AMP-activated protein kinase, inhibits non-proteolytic components of the 26S proteasome by an AMPK-independent mechanism
A769662, a novel activator of AMP-activated protein kinase, inhibits non-proteolytic components of the 26S proteasome by an AMPK-independent mechanism
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DOI：
10.1016/j.febslet.2008.06.044
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发表时间：
2008-07-23
期刊：
影响因子：
3.5
通讯作者：
Sanz, Pascual
中科院分区：
文献类型：
--
作者：
Moreno, Daniel;Knecht, Erwin;Sanz, Pascual
在这项工作中，我们提出的证据表明，A769662，一种新的激活剂的AMP激活的蛋白激酶（AMPK），能够抑制26 S蛋白酶体的功能，通过AMPK的非依赖性机制。与大多数蛋白酶体抑制剂的作用机制相反，A769662不影响20S核心亚基的蛋白水解活性。以这种方式产生抑制26S蛋白酶体活性的新机制。A769662对蛋白酶体活性的抑制是可逆的，并导致细胞周期进程停滞。当这种化合物用作激酶的替代激活剂时，应考虑这种新的AMPK激活剂的这些副作用。(C)2008年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
In this work we present evidence that A769662, a novel activator of AMP-activated protein kinase (AMPK), is able to inhibit the function of the 26S proteasome by an AMPK-independent mechanism. Contrary to the mechanism of action of most proteasome inhibitors, A769662 does not affect the proteolytic activities of the 20S core subunit, de. ning in this way a novel mechanism of inhibition of 26S proteasome activity. Inhibition of proteasome activity by A769662 is reversible and leads to an arrest of cell cycle progression. These side effects of this new activator of AMPK should be taken into account when this compound is used as an alternative activator of the kinase. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.