AMPKα2 activation by an energy-independent signal ensures chromosomal stability during mitosis.
AMPKα2 activation by an energy-independent signal ensures chromosomal stability during mitosis.
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AMPKα2 通过能量独立信号激活确保有丝分裂期间染色体的稳定性
DOI：
10.1016/j.isci.2021.102363
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发表时间：
2021-04-23
期刊：
影响因子：
5.8
通讯作者：
Yao X
中科院分区：
文献类型：
--
作者：
Lu J;Huang Y;Zhan L;Wang M;Xu L;Mullen M;Zang J;Fang G;Dou Z;Liu X;Liu W;Garcia-Barrio M;Yao X
AMP激活的蛋白激酶（AMPK）通过启动细胞内的代谢调节信号来感知能量状态并影响能量消耗事件。越来越多的证据表明AMPK在有丝分裂调控中的作用，但有丝分裂AMPK激活和功能的机制仍不清楚。在这里，我们报告AMPKα2，而不是AMPKα1，被CDK 1和PLK 1顺序磷酸化和激活，这使得AMPKα2能够准确地指导有丝分裂中的染色体分离。活化的CDK 1-Cyclin B1在Thr 485处的磷酸化将AMPKα2的ST-延伸带至PLK 1的波罗盒结构域，随后由PLK 1磷酸化Thr 172。将AMPKα2 ST段插入缺乏ST段的AMPKα1中，可以纠正AMPKα2缺失细胞中有丝分裂染色体分离缺陷。这些发现揭示了AMPKα2通过CDK 1和PLK 1的顺序磷酸化与有丝分裂整合以维持基因组稳定性的特异性信号级联，从而定义了亚型特异性AMPKα2功能，这将促进未来有丝分裂中能量感知的研究。AMPKα2在有丝分裂期间被CDK 1和PLK 1选择性激活AMPKα2中的保守基序决定其与PLK 1的相互作用和被PLK 1激活有丝分裂AMPK激活有助于维持正常有丝分裂中的基因组稳定性生物科学;细胞生物学;细胞
AMP-activated protein kinase (AMPK) senses energy status and impacts energy-consuming events by initiating metabolism regulatory signals in cells. Accumulating evidences suggest a role of AMPK in mitosis regulation, but the mechanism of mitotic AMPK activation and function remains elusive. Here we report that AMPKα2, but not AMPKα1, is sequentially phosphorylated and activated by CDK1 and PLK1, which enables AMPKα2 to accurately guide chromosome segregation in mitosis. Phosphorylation at Thr485 by activated CDK1-Cyclin B1 brings the ST-stretch of AMPKα2 to the Polo box domain of PLK1 for subsequent Thr172 phosphorylation by PLK1. Inserting of the AMPKα2 ST-stretch into AMPKα1, which lacks the ST-stretch, can correct mitotic chromosome segregation defects in AMPKα2-depleted cells. These findings uncovered a specific signaling cascade integrating sequential phosphorylation by CDK1 and PLK1 of AMPKα2 with mitosis to maintain genomic stability, thus defining an isoform-specific AMPKα2 function, which will facilitate future research on energy sensing in mitosis. AMPKα2 is selectively activated during mitosis by CDK1 and PLK1 A conserved motif in AMPKα2 determines its interaction with and activation by PLK1 Mitotic AMPK activation contributes to maintain genomic stability in normal mitosis Biological Sciences ; Cell Biology ; Cell
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DOI：
10.1083/jcb.129.6.1617
发表时间：
1995-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Golsteyn RM;Mundt KE;Fry AM;Nigg EA
通讯作者：
Nigg EA
DOI：
10.1006/bbrc.1994.1627
发表时间：
1994-05-16
影响因子：
3.1
作者：
SULLIVAN, JE;CAREY, F;BERI, RK
通讯作者：
BERI, RK
影响因子：
16
作者：
Banko, Max R.;Allen, Jasmina J.;Schaffer, Bethany E.;Wilker, Erik W.;Tsou, Peiling;White, Jamie L.;Villen, Judit;Wang, Beatrice;Kim, Sara R.;Sakamoto, Kei;Gygi, Steven P.;Cantley, Lewis C.;Yaffe, Michael B.;Shokat, Kevan M.;Brunet, Anne
通讯作者：
Brunet, Anne
影响因子：
11.8
作者：
Hutterer, Andrea;Berdnik, Daniela;Knoblich, Juergen A.
通讯作者：
Knoblich, Juergen A.
AMPK 磷酸化 GBF1 以促进有丝分裂高尔基体分解
影响因子：
4
作者：
Mao, Luna;Li, Ning;Liu, Wei
通讯作者：
Liu, Wei