HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Widodo, N. Articles by Kaul, S. C. Search for Related Content PubMed PubMed Citation Articles by Widodo, N. Articles by Kaul, S. C.

Stress Chaperones, Mortalin, and Pex19p Mediate 5-Aza-2' Deoxycytidine-Induced Senescence of Cancer Cells by DNA Methylation-Independent Pathway

¹ National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.
² Department of Molecular and Cellular Physiology, University of Tsukuba, Japan.
³ Department of Chemistry and Biotechnology, School of Engineering, University of Tokyo, Japan.
⁴ Cellular and Molecular Biology Group, Department of Radiobiology, Institute for Environmental Sciences, Aomori, Japan.

Address correspondence to Sunil C. Kaul, PhD, National Institute of Advanced Industrial Science & Technology (AIST), Central 4, 1-1-1, Higashi, Tsukuba, Ibaraki, 305-8562, Japan. E-mail: s-kaul{at}aist.go.jp

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.