title: Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α.
abstract: 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.
authors.affiliation: a Department of Oral Biology; College of Dentistry ; University of Nebraska Medical Center ; Lincoln , NE USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Guo
authors.forename: Laura A
authors.initials: LA
authors.lastname: Fisher
authors.forename: Dongxu
authors.initials: D
authors.lastname: Liu
authors.forename: Aimin
authors.initials: A
authors.lastname: Peng
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004249:DNA Damage; D007399:Interphase; D010063:Ovum / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014981:Xenopus / Q000254:growth & development; D029867:Xenopus Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D029867:Xenopus Proteins; D000097869:Polo-Like Kinase 1; C576898:Atr protein, Xenopus; C584831:ppp2r2a protein, Xenopus laevis
keywords: B55α; DNA damage; PP2A; Plk1; checkpoint recovery