Cell Cycle · 2014 · 35 citations · 34 references
Life SciencesCell BiologyMolecular BiologyDna RepairMolecular OncologySignal TransductionCell Cycle ControlCell-cycle CheckpointsCell-cycle RegulationDna DamageDna Damage SignalingProtein Kinase CascadesCheckpoint Recovery MechanismsDna Damage Checkpoint ActivationDna Damage Checkpoint KinasesDna Damage Checkpoint SignalingG2 Checkpoint ArrestPolo-like Kinase FunctionProtein DephosphorylationProtein Phosphatase 2A Regulation
In addition to governing mitotic progression, Plk1 also suppresses the activation of the G2 DNA damage checkpoint and promotes checkpoint recovery. Previous studies have shown that checkpoint activation after DNA damage requires inhibition of Plk1, but the underlying mechanism of Plk1 regulation was unknown. In this study we show that the specific phosphatase activity toward Plk1 Thr-210 in interphase Xenopus egg extracts is predominantly PP2A-dependent, and this phosphatase activity is upregulated by DNA damage. Consistently, PP2A associates with Plk1 and the association increases after DNA damage. We further revealed that B55α, a targeting subunit of PP2A and putative tumor suppressor, mediates PP2A/Plk1 association and Plk1 dephosphorylation. B55α and PP2A association is greatly strengthened after DNA damage in an ATM/ATR and checkpoint kinase-dependent manner. Collectively, we report a phosphatase-dependent mechanism that responds to DNA damage and regulates Plk1 and checkpoint recovery.
34
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
Christina Curtis, Sohrab P. Shah, Suet‐Feung Chin et al. · Nature · 2012 · 6.4K citations · Full text
Life Sciences, Genetics, Oncology +14
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
Libor Macůrek, Arne Lindqvist, Dan Lim et al. · Nature · 2008 · 711 citations
Polo-like kinase-1 is a target of the DNA damage checkpoint
Veronique A. J. Smits, Rob Klompmaker, Lionel Arnaud et al. · Nature Cell Biology · 2000 · 436 citations