β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression.

β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression.
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DOI:
10.1016/j.celrep.2018.08.076
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发表时间:
2018-09-25
期刊:
影响因子:
8.8
通讯作者:
D'Angiolella V
D'Angiolella V
中科院分区:
生物学1区
文献类型:
--
作者:
Mavrommati I;Faedda R;Galasso G;Li J;Burdova K;Fischer R;Kessler BM;Carrero ZI;Guardavaccaro D;Pagano M;D'Angiolella V

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细胞分裂周期中事件的有序进展是确保DNA复制和细胞分裂所必需的。检查点系统允许每个细胞周期阶段的准确执行。细胞周期蛋白水平的精确调节是协调细胞分裂与检查点,避免基因组不稳定的基础。细胞周期蛋白F在G2检查点期间调节细胞周期中具有重要功能;然而,对细胞周期蛋白F的调节机制知之甚少。在这里,我们观察到细胞周期蛋白F通过β-TrCP蛋白水解调节。β-TrCP在被酪蛋白激酶II磷酸化后通过非典型降解决定子位点(TSGXXS)识别细胞周期蛋白F。β-TrCP介导的细胞周期蛋白F降解发生在G2/M转换期。该事件是促进有丝分裂进程所必需的,并且有利于有丝分裂所需的转录程序的激活。β-TrCP 1和β-TrCP 2与细胞周期蛋白F相互作用,并在有丝分裂期间控制细胞周期蛋白F的水平。TSGXXS基序是β-TrCP 1和β-TrCP 2与细胞周期蛋白F结合所必需的。CKIIα在TSGXXS基序内的S704磷酸化细胞周期蛋白F。确定细胞周期蛋白F在有丝分裂过程中是如何通过蛋白水解调节的。细胞周期蛋白F在TSGXXS降解决定子内的S704上被CKII磷酸化后被β-TrCP泛素化。β-TrCP介导的细胞周期蛋白F降解通过控制B-Myb转录程序有利于及时的有丝分裂进程。
Orderly progressions of events in the cell division cycle are necessary to ensure the replication of DNA and cell division. Checkpoint systems allow the accurate execution of each cell-cycle phase. The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. Cyclin F has important functions in regulating the cell cycle during the G2 checkpoint; however, the mechanisms underlying the regulation of cyclin F are poorly understood. Here, we observe that cyclin F is regulated by proteolysis through β-TrCP. β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. This event is required to promote mitotic progression and favors the activation of a transcriptional program required for mitosis. β-TrCP1 and β-TrCP2 interact with cyclin F and control cyclin F levels during mitosis A TSGXXS motif is necessary for β-TrCP1 and β-TrCP2 binding to cyclin F CKIIα phosphorylates cyclin F at S704 within the TSGXXS motif β-TrCP-mediated degradation of cyclin F promotes mitotic progression via B-Myb Mavrommati et al. identify how cyclin F is regulated during mitosis by proteolysis. Cyclin F is ubiquitylated by β-TrCP after phosphorylation by CKII on S704 within a TSGXXS degron. β-TrCP-mediated degradation of cyclin F favors timely mitotic progression through the control of a B-Myb transcriptional program.
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