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Published on: August 4, 2019
Retrotransposition-Competent Human LINE-1 Induces Apoptosis in Cancer Cells With Intact p53
Abstract:
Retrotransposition of human LINE-1 (L1) element, a major representative non-LTR retrotransposon in the human genome, is known to be a source of insertional mutagenesis. However, nothing is known about effects of L1 retrotransposition on cell growth and differentiation. To investigate the potential for such biological effects and the impact that human L1 retrotransposition has upon cancer cell growth, we examined a panel of human L1 transformed cell lines following a complete retrotransposition process. The results demonstrated that transposition of L1 leads to the activation of the p53-mediated apoptotic pathway in human cancer cells that possess a wild-type p53. In addition, we found that inactivation of p53 in cells, where L1 was undergoing retrotransposition, inhibited the induction of apoptosis. This suggests an association between active retrotransposition and a competent p53 response in which induction of apoptosis is a major outcome. These data are consistent with a model in which human retrotransposition is sensed by the cell as a "genetic damaging event" and that massive retrotransposition triggers signaling pathways resulting in apoptosis.
Insights
Human LINE-1 (L1) retrotransposition activates the p53 apoptotic pathway in cancer cells. Inactivating p53 prevents this apoptosis, suggesting L1 transposition is recognized as DNA damage.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Human LINE-1 (L1) elements are non-LTR retrotransposons.
- L1 retrotransposition is a known cause of insertional mutagenesis.
- The effects of L1 retrotransposition on cell growth and differentiation are largely unknown.
Purpose of the Study:
- To investigate the biological effects of L1 retrotransposition on cell growth.
- To determine the impact of human L1 retrotransposition on cancer cell growth.
- To explore the relationship between L1 transposition and cancer cell pathways.
Main Methods:
- Examined human cancer cell lines with complete L1 retrotransposition.
- Assessed the p53-mediated apoptotic pathway.
- Investigated the role of p53 status (wild-type vs. inactivated) in apoptosis induction.
Main Results:
- L1 retrotransposition activates the p53-mediated apoptotic pathway in cancer cells with wild-type p53.
- Inactivation of p53 inhibits apoptosis induction during L1 retrotransposition.
- Suggests a strong association between active L1 retrotransposition and p53-dependent apoptosis.
Conclusions:
- Human L1 retrotransposition is recognized by cells as a "genetic damaging event".
- Massive retrotransposition triggers signaling pathways leading to apoptosis.
- L1 retrotransposition impacts cancer cell fate through the p53 pathway.
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