Hip2 ubiquitin-conjugating enzyme overcomes radiation-induced G2/M arrest

Yoonhee Bae, Song Hwa Jung, Goo Young Kim, Hyangshuk Rhim, Seong Man Kang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Radiation induces cell cycle arrest and/or cell death in mammalian cells. In the present study, we show that Hip2, a ubiquitin-conjugating enzyme, can overcome radiation-induced G2/M cell cycle arrest and trigger the entry into mitosis. Ionizing radiation increased the levels of Hip2 by preventing its degradation but not its gene transcription. The stability of Hip2 in irradiated cells was further confirmed using live cell fluorescence imaging. Flow cytometric and molecular analyses revealed that Hip2 abrogated radiation-induced G2/M arrest, promoting entry into mitosis. Bimolecular fluorescence complementation assays and co-immunoprecipitation experiments showed that Hip2 interacted with and targeted p53 for degradation via the ubiquitin proteasome system, resulting in the activation of cdc2-cyclin B1 kinase to promote mitotic entry. These results contribute to our understanding of the mechanisms that regulate cell cycle progression and DNA damage-induced G2/M checkpoint cellular responses.

Original languageEnglish
Pages (from-to)2911-2921
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number12
DOIs
Publication statusPublished - 2013 Dec 1

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Keywords

  • G2/M arrest
  • Hip2
  • P53
  • Radiation
  • Ubiquitination

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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