Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α

Ling Wang, Qingyuan Guo, Laura A. Fisher, Dongxu Liu, Aimin Peng

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 PP2Adependent, 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.

Original languageEnglish (US)
Pages (from-to)157-166
Number of pages10
JournalCell Cycle
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

DNA Damage
Phosphoric Monoester Hydrolases
Interphase
Xenopus
Ovum
polo-like kinase 1
Phosphotransferases
Neoplasms

Keywords

  • B55a
  • Checkpoint recovery
  • DNA damage
  • PP2A
  • Plk1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α. / Wang, Ling; Guo, Qingyuan; Fisher, Laura A.; Liu, Dongxu; Peng, Aimin.

In: Cell Cycle, Vol. 14, No. 1, 01.01.2015, p. 157-166.

Research output: Contribution to journalArticle

Wang, Ling ; Guo, Qingyuan ; Fisher, Laura A. ; Liu, Dongxu ; Peng, Aimin. / Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α. In: Cell Cycle. 2015 ; Vol. 14, No. 1. pp. 157-166.
@article{211bee0093f34a8f98a3c0081ada72c3,
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 PP2Adependent, 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.",
keywords = "B55a, Checkpoint recovery, DNA damage, PP2A, Plk1",
author = "Ling Wang and Qingyuan Guo and Fisher, {Laura A.} and Dongxu Liu and Aimin Peng",
year = "2015",
month = "1",
day = "1",
doi = "10.4161/15384101.2014.986392",
language = "English (US)",
volume = "14",
pages = "157--166",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "1",

}

TY - JOUR

T1 - Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α

AU - Wang, Ling

AU - Guo, Qingyuan

AU - Fisher, Laura A.

AU - Liu, Dongxu

AU - Peng, Aimin

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 PP2Adependent, 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.

AB - 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 PP2Adependent, 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.

KW - B55a

KW - Checkpoint recovery

KW - DNA damage

KW - PP2A

KW - Plk1

UR - http://www.scopus.com/inward/record.url?scp=84929461224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929461224&partnerID=8YFLogxK

U2 - 10.4161/15384101.2014.986392

DO - 10.4161/15384101.2014.986392

M3 - Article

VL - 14

SP - 157

EP - 166

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 1

ER -