Cyclin G1 associates with MDM2 and regulates accumulation and degradation of p53 protein.
BACKGROUND
Cyclin G1 is a transcriptional target of p53 and is induced by DNA damage in a p53 dependent manner. Analysis of cyclin G1 disrupted mice demonstrated that cyclin G1 is involved in many of the functions regulated by p53 such as apoptosis, growth control and check point regulation in response to DNA damage. The results suggest that the main role of cyclin G1 is to mediate or regulate the function of p53.


RESULTS
Western blot analysis revealed that the accumulation of p53 protein during the initial 24 h period following DNA damage is reduced in cyclin G1-/- cells compared to wild-type cells. This decrease in p53 accumulation could be recovered by introducing a cDNA expressing cyclin G1. Cyclin G1 interacted directly with MDM2 and promoted the formation of the ARF/MDM2 complex within the initial 24 h period following DNA damage. Furthermore, 48 h after irradiation, accumulation of p53 protein was enhanced in cyclin G1-/- cells compared to wild-type cells. In contrast, in 48 h postirradiated wild-type cells, the cyclin G1-MDM2 complex was found not to be associated with ARF but with the B'alpha subunit of protein phosphatase A.


CONCLUSIONS
These results suggest that cyclin G1 stabilizes and promotes the degradation of p53 protein by associating, respectively, with MDM2 complexes containing ARF and PP2A.
Kimura
Shinya H
SH
Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nojima
Hiroshi
H
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins; D006868:Hydrolysis; D051379:Mice; D009687:Nuclear Proteins; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
C534703:Ccng1 protein, mouse; D018797:Cell Cycle Proteins; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases