The evolutionarily conserved Cdc25 phosphatase is an essential protein that removes inhibitory phosphorylation moieties on the mitotic regulator Cdc2. Together with the Wee1 kinase, a negative regulator of Cdc2 activity, Cdc25 is thus a central regulator of cell cycle progression in Schizosaccharomyces pombe. The expression and activity of Cdc25 is dependent on the activity of the Target of Rapamycin Complex 1 (TORC1). TORC1 inhibition leads to the activation of Cdc25 and repression of Wee1, leading to advanced entry into mitosis. Withdrawal of nitrogen leads to rapid Cdc25 degradation via the ubiquitin- dependent degradation pathway by the Pub1 E3- ligase. Caffeine is believed to mediate the override of DNA damage checkpoint signalling, by inhibiting the activity of the ataxia telangiectasia mutated (ATM)/Rad3 homologues. This model remains controversial, as TORC1 appears to be the preferred target of caffeine in vivo. Recent studies suggest that caffeine induces DNA damage checkpoint override by inducing the nuclear accumulation of Cdc25 in S. pombe. Caffeine may thus modulate Cdc25 activity and stability via inhibition of TORC1. A clearer understanding of the mechanisms by which caffeine stabilises Cdc25, may provide novel insights into how TORC1 and DNA damage signalling is integrated.

中文翻译：

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咖啡因是研究粟酒裂殖酵母中Cdc25磷酸化，活性和泛素依赖性降解整合的一种工具。

进化保守的Cdc25磷酸酶是一种必需蛋白，可去除有丝分裂调节剂Cdc2上的抑制性磷酸化部分。因此，与Wee1激酶（Cdc2活性的负调节剂）一起，Cdc25是粟酒裂殖酵母中细胞周期进程的中央调节剂。Cdc25的表达和活性取决于雷帕霉素复合物1（TORC1）靶标的活性。TORC1的抑制导致Cdc25的激活和Wee1的抑制，导致晚期进入有丝分裂。氮的吸收导致Pub1 E3-连接酶通过泛素依赖性降解途径快速导致Cdc25降解。据信咖啡因可通过抑制共济失调毛细血管扩张突变（ATM）/ Rad3同源物的活性来介导DNA损伤检查点信号。该模型仍然存在争议，因为TORC1似乎是体内咖啡因的首选靶标。最近的研究表明，咖啡因通过诱导粟酒裂殖酵母中Cdc25的核积累来诱导DNA损伤检查点超控。因此，咖啡因可通过抑制TORC1来调节Cdc25活性和稳定性。对咖啡因稳定Cdc25的机制的更清晰的了解可能为TORC1和DNA损伤信号转导的整合方式提供新颖的见解。