Cyclin F is degraded during G2-M by mechanisms fundamentally different from other cyclins
Cyclin F is degraded during G2-M by mechanisms fundamentally different from other cyclins
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DOI：
10.1074/jbc.m205503200
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发表时间：
2002-09-20
影响因子：
4.8
通讯作者：
Poon, RYC
中科院分区：
文献类型：
--
作者：
Fung, TK;Sin, WY;Poon, RYC
细胞周期蛋白 F 是一种细胞周期蛋白，可以形成 SCF 复合物并与细胞周期蛋白 B 结合，在细胞周期中以类似于细胞周期蛋白 A 和细胞周期蛋白 B 的模式振荡。细胞周期蛋白 F 的异位表达使细胞周期停滞在 G(2)/M 阶段。细胞周期中细胞周期蛋白 F 的水平如何受到调节尚不清楚。在这里，我们发现，与细胞周期蛋白 A 类似，细胞周期蛋白 F 在纺锤体组装检查点激活时降解，并在 DNA 损伤检查点激活时积累。细胞周期蛋白 F 在整个细胞周期的大部分时间里都是一种非常不稳定的蛋白质。与其他细胞周期蛋白不同，细胞周期蛋白 F 的降解独立于泛素化和蛋白酶体介导的途径。有趣的是，细胞周期蛋白 F 的蛋白水解很可能涉及金属蛋白酶。细胞周期蛋白 F 的快速破坏不需要 N 端 F-box 基序，但需要 COOH 端 PEST 序列。单独的 PEST 区域足以干扰细胞周期蛋白 F 的降解，并在与细胞周期蛋白 A 融合时赋予稳定性。这些数据表明，尽管细胞周期蛋白 F 与有丝分裂细胞周期蛋白在相似的时间降解，但潜在的机制完全不同。
Cyclin F, a cyclin that can form SCF complexes and bind to cyclin B, oscillates in the cell cycle with a pattern similar to cyclin A and cyclin B. Ectopic expression of cyclin F arrests the cell cycle in G(2)/M. How the level of cyclin F is regulated during the cell cycle is completely obscure. Here we show that, similar to cyclin A, cyclin F is degraded when the spindle assembly checkpoint is activated and accumulates when the DNA damage checkpoint is activated. Cyclin F is a very unstable protein throughout much of the cell cycle. Unlike other cyclins, degradation of cyclin F is independent of ubiquitination and proteasome-mediated pathways. Interestingly, proteolysis of cyclin F is likely to involve metalloproteases. Rapid destruction of cyclin F does not require the N-terminal F-box motif but requires the COOH-terminal PEST sequences. The PEST region alone is sufficient to interfere with the degradation of cyclin F and confer instability when fused to cyclin A. These data show that although cyclin F is degraded at similar time as the mitotic cyclins, the underlying mechanisms are entirely distinct.