Integrating Old and New Paradigms of G1/S Control.

Integrating Old and New Paradigms of G1/S Control.
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DOI:
10.1016/j.molcel.2020.08.020
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发表时间:
2020-10-15
期刊:
影响因子:
16
通讯作者:
Skotheim JM
Skotheim JM
中科院分区:
生物学1区
文献类型:
--
作者:
Rubin SM;Sage J;Skotheim JM

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Cdk-Rb-E2 F通路整合外部和内部信号以控制哺乳动物细胞周期的G1/S转换的进展。在绝大多数人类癌症中发现了该途径的改变,并且特定的Cdk 4/6抑制剂被批准或在临床试验中用于治疗多种癌症。在长期存在的G1/S控制模式中,Cdks通过磷酸化作用修饰Rb,从而释放E2 F转录因子,驱动细胞周期从G1期进展到S期。然而,最近在实验室和临床上的观察挑战了当前范式的中心原则,并表明我们对Rb通路和G1/S控制的理解仍然是不完整的。在这里,我们将这些最新的研究结果与以前的范例,以综合目前的哺乳动物G1/S过渡的分子和细胞的观点。对G1/S控制的更完整和准确的理解将最终导致针对癌症细胞周期的治疗策略的改进。
The Cdk-Rb-E2F pathway integrates external and internal signals to control progression at the G1/S transition of the mammalian cell cycle. Alterations in this pathway are found in the vast majority of human cancers and specific Cdk4/6 inhibitors are approved or in clinical trials for the treatment of diverse cancers. In the long-standing paradigm for G1/S control, Cdks inactivate Rb through phosphorylation, which releases E2F transcription factors to drive cell-cycle progression from G1 to S. However, recent observations in the laboratory and clinic challenge central tenets of the current paradigm and demonstrate that our understanding of the Rb pathway and G1/S control is still incomplete. Here, we integrate these recent findings with the previous paradigm to synthesize a current molecular and cellular view of the mammalian G1/S transition. A more complete and accurate understanding of G1/S control will ultimately lead to improved therapeutic strategies targeting the cell cycle in cancer.
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