Stress chaperones, mortalin, and pex19p mediate 5-aza-2' deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathway. The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] Journal article | | Title | Stress chaperones, mortalin, and pex19p mediate 5-aza-2' deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathway. | | Author(s) | Widodo N, Deocaris CC, Kaur K, Hasan K, Yaguchi T, Yamasaki K, Sugihara T, Ishii T, Wadhwa R, Kaul SC | | Institution | National Institute of Advanced Industrial Science & Technology (AIST), Central 4, 1-1-1, Higashi, Tsukuba, Ibaraki, Japan. | | Source | J Gerontol A Biol Sci Med Sci 2007 Mar; 62(3):246-55. | | 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, Pex19p 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 p16(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 Pex19p are important mediators, prognostic indicators, and tailoring tools for 5AZA-dC-induced senescence in cancer cells. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 17389721 |
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