Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1.
Although cyclin G1 has been implicated in certain p53-related biological phenomena, other aspects of its function remain unclear. Here we report hitherto unknown mechanism by which cyclin G1 increases radiation sensitivity by regulating the level of cyclin B1. Overexpression of cyclin G1 was observable in lung carcinoma tissues. Irradiation of human lung cells with cyclin G1 overexpression resulted in increased cell death and gamma-H2AX foci suggesting that cyclin G1 rendered the cells more susceptible to DNA damage. Enhanced radiosensitivity by cyclin G1 was correlated with increased cyclin B1, CDC2/cyclin B1 complex, and MPM2. Cell cycle synchronization clearly showed coexpression of cyclin G1 and cyclin B1 in G2/M phase. Depletion of cyclin G1 by interference RNA revealed that cyclin G1 regulated transcription of cyclin B1 in a p53-independent manner, and confirmed that the increased mitotic cells and cell death by cyclin G1 were dependent upon cyclin B1. Therefore, our data suggest that cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1.
Seo
H R
HR
Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Korea.
Lee
D H
DH
Lee
H J
HJ
Baek
M
M
Bae
S
S
Soh
J W
JW
Lee
S J
SJ
Kim
J
J
Lee
Y S
YS
D000231:Adenocarcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000096:biosynthesis*; D056744:Cyclin B1; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000096:biosynthesis / Q000502:physiology*; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C534699:CCNB1 protein, human; C534702:CCNG1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase