A role of cyclin G in the process of apoptosis.
Cyclin G was previously identified as a target gene of the p53 tumor suppresser protein, and levels of cyclin G are increased after induction of p53 by DNA damage. However, the function of cyclin G has not been established. To determine the effect of increased expression of cyclin G, retroviruses encoding cyclin G were constructed and used to infect three different murine cell lines. Cyclin G protein levels induced by the retroviruses were within the range seen after DNA damage induction of p53. In each case we observed that such over-expression of cyclin G augments the apoptotic process. TNF-alpha induction of apoptosis is increased by expression of cyclin G in NIH3T3 fibroblasts which express p53, as well as in 10.1 fibroblasts which contain no p53 allele. Additionally, we observed that while cyclin G expression is markedly reduced upon aggregate formation in embryonic carcinoma P19 cells, retrovirus-mediated over-expression of cyclin G enhances apoptotic cell death in aggregated P19 cells, and increases the extent of apoptosis caused by retinoic acid or serum starvation of these cells. These data demonstrate that cyclin G plays a facilitating role in modulating apoptosis induced by different stimuli. Moreover, we have discovered that cyclin G expression is rapidly induced in P19 cells after exposure to Bone Morphogenic Protein-4 (BMP-4), suggesting that cyclin G may mediate apoptotic signals generated by BMP-4.
Okamoto
K
K
Columbia University, Department of Biological Sciences, New York, NY 10027, USA.
Prives
C
C
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051379:Mice; D012190:Retroviridae; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C534703:Ccng1 protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D014409:Tumor Necrosis Factor-alpha