Polo-like kinase 1 coordinates biosynthesis during cell cycle progression by directly activating pentose phosphate pathway.
Polo-like kinase 1 coordinates biosynthesis during cell cycle progression by directly activating pentose phosphate pathway.
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Polo 样激酶 1 通过直接激活磷酸戊糖途径协调细胞周期进程中的生物合成
DOI：
10.1038/s41467-017-01647-5
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发表时间：
2017-11-15
影响因子：
16.6
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Ma X;Wang L;Huang D;Li Y;Yang D;Li T;Li F;Sun L;Wei H;He K;Yu F;Zhao D;Hu L;Xing S;Liu Z;Li K;Guo J;Yang Z;Pan X;Li A;Shi Y;Wang J;Gao P;Zhang H
癌细胞的两个标志是加速的细胞周期进程以及改变的代谢，然而，这些变化如何协调以优化癌细胞的生长优势仍然知之甚少。在这里，我们确定Polo样激酶1（Plk 1），细胞有丝分裂的关键调节因子，通过激活磷酸戊糖途径（PPP）在癌细胞的生物合成中起着关键作用。我们发现Plk 1与葡萄糖-6-磷酸脱氢酶（G6 PD）相互作用并直接磷酸化。Plk 1通过促进其活性二聚体的形成来激活G6 PD，从而增加PPP通量并指导葡萄糖合成大分子。重要的是，我们进一步证明了Plk 1介导的G6 PD激活对于其促进细胞周期进展和癌细胞生长的作用至关重要。总的来说，这些发现确立了Plk 1在调节癌细胞生物合成中的关键作用，举例说明了细胞周期进展和代谢重编程如何协调癌症进展。
Two hallmarks for cancer cells are the accelerated cell cycle progression as well as the altered metabolism, however, how these changes are coordinated to optimize the growth advantage for cancer cells are still poorly understood. Here we identify that Polo-like kinase 1 (Plk1), a key regulator for cell mitosis, plays a critical role for biosynthesis in cancer cells through activating pentose phosphate pathway (PPP). We find that Plk1 interacts with and directly phosphorylates glucose-6-phosphate dehydrogenase (G6PD). By activating G6PD through promoting the formation of its active dimer, Plk1 increases PPP flux and directs glucose to the synthesis of macromolecules. Importantly, we further demonstrate that Plk1-mediated activation of G6PD is critical for its role to promote cell cycle progression and cancer cell growth. Collectively, these findings establish a critical role for Plk1 in regulating biosynthesis in cancer cells, exemplifying how cell cycle progression and metabolic reprogramming are coordinated for cancer progression.
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影响因子：
7.5
作者：
Lee, In Hye;Finkel, Toren
通讯作者：
Finkel, Toren
影响因子：
9.7
作者：
Gutteridge RE;Singh CK;Ndiaye MA;Ahmad N
通讯作者：
Ahmad N
影响因子：
64.8
作者：
Lee, Yoonjin;Dominy, John E.;Choi, Yoon Jong;Jurczak, Michael;Tolliday, Nicola;Camporez, Joao Paulo;Chim, Helen;Lim, Ji-Hong;Ruan, Hai-Bin;Yang, Xiaoyong;Vazquez, Francisca;Sicinski, Piotr;Shulman, Gerald I.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
64.5
作者：
Atilla-Gokcumen GE;Muro E;Relat-Goberna J;Sasse S;Bedigian A;Coughlin ML;Garcia-Manyes S;Eggert US
通讯作者：
Eggert US
影响因子：
16
作者：
Düvel K;Yecies JL;Menon S;Raman P;Lipovsky AI;Souza AL;Triantafellow E;Ma Q;Gorski R;Cleaver S;Vander Heiden MG;MacKeigan JP;Finan PM;Clish CB;Murphy LO;Manning BD
通讯作者：
Manning BD