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Stress chaperones, mortalin, and Pex19p mediate 5-Aza-2' deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathway
- Source :
- The Journals of Gerontology, Series A. March, 2007, Vol. 62 Issue 3, p246, 10 p.
- Publication Year :
- 2007
-
Abstract
- DNA demethylating agents are used to reverse epigenetic silencing of tumor suppressors in cancer therapeutics. Understanding of the molecular and cellular factors involved in DNA demethylation-induced gene desilencing and senescence is still limited. We have tested the involvement of two stress chaperones, Pexl9p and mortalin, in 5-Aza-2' deoxycytidine (5AZA-dC; DNA demethylating agent)-induced senescence. We found that the cells overexpressing these chaperones were highly sensitive to 5AZA-dC, and their partial silencing eliminated 5AZA-dC-induced senescence in human osteosarcoma cells. We demonstrate that these chaperones modulate the demethylation and chromatin remodeling-dependent (as accessed by p[16.sup.INK4A] expression) and remodeling-independent (such as activation of tumor suppressor p53 pathway) senescence response of cells. Furthermore, we found the direct interactions of 5AZA-dC with these chaperones that may alter their functions. We conclude that both mortalin and Pexl9p are important mediators, prognostic indicators, and tailoring tools for 5AZA-dC-induced senescence in cancer cells.
Details
- Language :
- English
- ISSN :
- 10795006
- Volume :
- 62
- Issue :
- 3
- Database :
- Gale General OneFile
- Journal :
- The Journals of Gerontology, Series A
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.173970081