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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.
Bartek,
DNA damage checkpoints: from initiation to recovery or adaptation.
2007, Pubmed
Bartek,
DNA damage checkpoints: from initiation to recovery or adaptation.
2007,
Pubmed
Cheng,
Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study.
2011,
Pubmed
Cristóbal,
PP2A inhibition is a common event in colorectal cancer and its restoration using FTY720 shows promising therapeutic potential.
2014,
Pubmed
Curtis,
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.
2012,
Pubmed
Eckerdt,
Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A.
2009,
Pubmed
,
Xenbase
Eckerdt,
Polo-like kinases and oncogenesis.
2005,
Pubmed
Jang,
Regulation of Polo-like kinase 1 by DNA damage in mitosis. Inhibition of mitotic PLK-1 by protein phosphatase 2A.
2007,
Pubmed
Janssen,
Mitosis as an anti-cancer target.
2011,
Pubmed
Jin,
Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma.
2006,
Pubmed
Kachaner,
Plk1-dependent phosphorylation of optineurin provides a negative feedback mechanism for mitotic progression.
2012,
Pubmed
Kalev,
Loss of PPP2R2A inhibits homologous recombination DNA repair and predicts tumor sensitivity to PARP inhibition.
2012,
Pubmed
Khanna,
DNA double-strand breaks: signaling, repair and the cancer connection.
2001,
Pubmed
Krystyniak,
Inhibition of Aurora A in response to DNA damage.
2006,
Pubmed
Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase
Lee,
Mitotic DNA damage response: Polo-like kinase-1 is dephosphorylated through ATM-Chk1 pathway.
2010,
Pubmed
Lee,
Plk is a functional homolog of Saccharomyces cerevisiae Cdc5, and elevated Plk activity induces multiple septation structures.
1997,
Pubmed
,
Xenbase
Lens,
Shared and separate functions of polo-like kinases and aurora kinases in cancer.
2010,
Pubmed
Li,
A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55.
2007,
Pubmed
Lindqvist,
The decision to enter mitosis: feedback and redundancy in the mitotic entry network.
2009,
Pubmed
Liu,
Homozygous deletions and recurrent amplifications implicate new genes involved in prostate cancer.
2008,
Pubmed
Liu,
Xenopus Polo-like kinase Plx1: a multifunctional mitotic kinase.
2005,
Pubmed
,
Xenbase
Liu,
Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor.
2005,
Pubmed
,
Xenbase
Ma,
How protein kinases co-ordinate mitosis in animal cells.
2011,
Pubmed
Macůrek,
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery.
2008,
Pubmed
Mamely,
Polo-like kinase-1 controls proteasome-dependent degradation of Claspin during checkpoint recovery.
2006,
Pubmed
Marumoto,
Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells.
2002,
Pubmed
,
Xenbase
Melo,
A unified view of the DNA-damage checkpoint.
2002,
Pubmed
,
Xenbase
Mochida,
Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts.
2009,
Pubmed
,
Xenbase
Mosca,
Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.
2013,
Pubmed
Motoyama,
DNA damage tumor suppressor genes and genomic instability.
2004,
Pubmed
Peng,
Undamaged DNA transmits and enhances DNA damage checkpoint signals in early embryos.
2007,
Pubmed
,
Xenbase
Peng,
Repo-man controls a protein phosphatase 1-dependent threshold for DNA damage checkpoint activation.
2010,
Pubmed
,
Xenbase
Peng,
A novel role for greatwall kinase in recovery from DNA damage.
2010,
Pubmed
,
Xenbase
Peng,
Serine/threonine phosphatases in the DNA damage response and cancer.
2010,
Pubmed
Peng,
Greatwall and Polo-like kinase 1 coordinate to promote checkpoint recovery.
2011,
Pubmed
,
Xenbase
Peschiaroli,
SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response.
2006,
Pubmed
Seki,
Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry.
2008,
Pubmed
,
Xenbase
Shen,
Upregulation of miR-136 in human non-small cell lung cancer cells promotes Erk1/2 activation by targeting PPP2R2A.
2014,
Pubmed
Shiloh,
ATM and related protein kinases: safeguarding genome integrity.
2003,
Pubmed
Smits,
Polo-like kinase-1 is a target of the DNA damage checkpoint.
2000,
Pubmed
Takaki,
Polo-like kinase 1 reaches beyond mitosis--cytokinesis, DNA damage response, and development.
2008,
Pubmed
Taylor,
Polo and Aurora kinases: lessons derived from chemical biology.
2008,
Pubmed
Tsvetkov,
Phosphorylation of Plk1 at S137 and T210 is inhibited in response to DNA damage.
2005,
Pubmed
Vagnarelli,
Repo-Man coordinates chromosomal reorganization with nuclear envelope reassembly during mitotic exit.
2011,
Pubmed
Virshup,
From promiscuity to precision: protein phosphatases get a makeover.
2009,
Pubmed
Yamashiro,
Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1.
2008,
Pubmed
Yoo,
Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase.
2004,
Pubmed
,
Xenbase
Zhou,
The DNA damage response: putting checkpoints in perspective.
2000,
Pubmed
van Vugt,
A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint.
2010,
Pubmed
van Vugt,
Polo-like kinase-1 controls recovery from a G2 DNA damage-induced arrest in mammalian cells.
2004,
Pubmed
