Hip2 ubiquitin-conjugating enzyme overcomes radiation-induced G2/M arrest.
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.
Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
Yoonhee
Y
Bae
Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
Song Hwa
SH
Jung
Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701, Republic of Korea.
Goo-Young
GY
Kim
Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701, Republic of Korea. Electronic address: hrhim@catholic.ac.kr.
Hyangshuk
H
Rhim
Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea. Electronic address: skang@korea.ac.kr.
Seongman
S
Kang
D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D008938:Mitosis / Q000528:radiation effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D055550:Protein Stability / Q000528:radiation effects; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C100879:UBE2K protein, human; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex
G2/M arrest; Hip2; Radiation; Ubiquitination; p53