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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
A role of cyclin G in the process of apoptosis
1Columbia University, Department of Biological Sciences, New York, NY 10027, USA.
Abstract:
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.
Insights
Cyclin G facilitates apoptosis, a programmed cell death process, across various cell types and stimuli. This protein
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Cyclin G is a target gene of the p53 tumor suppressor protein.
- Cyclin G levels increase following p53 induction by DNA damage.
- The precise function of Cyclin G has remained largely unelucidated.
Purpose of the Study:
- To investigate the functional role of Cyclin G in cellular processes.
- To determine the effects of increased Cyclin G expression on apoptosis.
Main Methods:
- Retroviral vectors were engineered to overexpress Cyclin G in murine cell lines.
- Cyclin G protein levels were confirmed to be within physiological ranges post-induction.
- Apoptosis was assessed in response to various stimuli, including TNF-alpha, retinoic acid, serum starvation, and Bone Morphogenic Protein-4 (BMP-4).
Main Results:
- Overexpression of Cyclin G augmented the apoptotic process in all tested cell lines.
- Cyclin G enhanced TNF-alpha-induced apoptosis in both p53-expressing and p53-deficient cells.
- Cyclin G overexpression increased apoptosis in aggregated P19 cells and potentiated apoptosis induced by retinoic acid or serum starvation.
- Cyclin G expression was rapidly induced by BMP-4 in P19 cells, suggesting a role in BMP-4 signaling.
Conclusions:
- Cyclin G plays a facilitating role in modulating apoptosis induced by diverse stimuli.
- Cyclin G may mediate apoptotic signals triggered by Bone Morphogenic Protein-4 (BMP-4).
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