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Cell Cycle. 2006 Oct;5(20):2319-23. Epub 2006 Oct 16.

Cellular senescence, epigenetic switches and c-Myc.

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Department of Molecular Biology, Cell Biology and Biochemistry, Center for Genomics and Proteomics, Brown University, Providence, Rhode Island, USA.


In response to hyperproliferative signaling elicited by transforming oncogenes some normal human cells can enter replicative senescence as a tumor defense mechanism. We recently found that human fibroblasts or endothelial cells with genetically-engineered reduction of proto-oncogene c-Myc expression switched with an increased frequency to a senescent state by a telomere-independent mechanism involving the polycomb group repressor Bmi-1 and the cyclin-dependent kinase inhibitor p16(INK4a). The same regulatory circuit was triggered upon exposure to mild oxidative stress. These findings point to the existence of a mechanism for monitoring hypoproliferative signaling, whose function may be to limit the proliferation and accretion of physiologically compromised cells. This mechanism may be another example of antagonistic pleiotropy leading to organismal aging.

[Indexed for MEDLINE]

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