A role of cyclin G in the process of apoptosis

Oncogene. 1999 Aug 12;18(32):4606-15. doi: 10.1038/sj.onc.1202821.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis*
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Line
  • Cyclin G
  • Cyclin G1
  • Cyclins / biosynthesis
  • Cyclins / genetics
  • Cyclins / physiology*
  • Down-Regulation
  • Gene Transfer Techniques
  • Genetic Vectors
  • Mice
  • Retroviridae
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Ccng1 protein, mouse
  • Cyclin G
  • Cyclin G1
  • Cyclins
  • Tumor Necrosis Factor-alpha