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(PP233) Cyclin G1 dacilitates radiation-induced G2-M transition and cell death through transcriptional activation of Cyclin B1.
Seo, Haeng Ran1, Lee, Dae-Hoon 1, Bae, Sangwoo1, Soh, Jae-Won 2, Lee, Yun-Sil 1, 1 Laboratory of Radiation Effect, Seoul, Nowon-Gu, Korea2 Laboratory of Signal Transduction, Incheon, Nam-Gu, Korea
ABSTRACT- Cyclin G1 is frequently overexpressed in cancer tissues and a target genes of the transcription factor p53, and is induced in a p53-depedent manner in response to DNA damage. Although cyclin G1 has been implicated in a range of biological phenomena which are usually connected with p53, other functions independent to p53 remain unclear. Immunocytostaining using tissue array reveals that cyclin G1 was overexpressed in lung carcinoma tissues when compared to corresponding normal tissue. Overexpression of cyclin G1 in human lung cells such as NCI-H460 and WI38 which cells relatively low expressed cyclin G1, increased radiation-induced clonogenic inhibition and cell death which were linked with susceptibility of radiation mediated damage; cycline G1 reduced radiation-induced phosphorylation of H2AX. Increased radiation-induced G2-M transition with increased MPM2 expression was shown by cyclin G1 overexpression. Cyclin B1, central regulator fro progression from G2 to mitosis, was also increased with increased its complex with CDC2 kinase, while the expressions of Cip1/p21 and Kip1/p27, inhibitor of CDK were reduced by cyclin G1 overexpression. Mimosine treatment for arresting G1 phase cell cycle revealed that cyclin G1 expression was evident in G2/M phase in accordance with increased induction of cyclin B1. Treatment of cyclin G1 Si-RNA revealed that cyclin G1 regulated cyclin B1 expression which was independent of p53 expression, and increased G2-M transition and cell death by cyclin G1 was abrogated. Moreover, cyclin B1 expression by cyclin G1 was regulated transcriptionally. The data suggested that cyclin G1 increased radiation-induced G2-M transition and cell death which is mediated by transcriptional activation of cyclin B1.
Key words: cyclin G1, G2-M Transition, cyclin B1
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