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Perspectives

Cellular Senescence, Epigenetic Switches and c-Myc

Isil Guney and John Sedivy

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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.

Authors

Isil Guney

Center for Genomics and Proteomics; Brown University , Providence RI, USA and Dana-Farber Cancer Institute; Boston, Massachusetts USA

John Sedivy

Center for Genomics and Proteomics; Brown University, Providence, Rhode Island USA

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.