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Originally published In Press as doi:10.1074/jbc.M609267200 on November 29, 2006

J. Biol. Chem., Vol. 282, Issue 7, 4702-4710, February 16, 2007
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Differential Effects of Endoplasmic Reticulum Stress-induced Autophagy on Cell Survival*

Wen-Xing Ding{ddagger}1, Hong-Min Ni{ddagger}, Wentao Gao{ddagger}, Yi-Feng Hou{ddagger}§, Melissa A. Melan{ddagger}, Xiaoyun Chen{ddagger}, Donna B. Stolz, Zhi-Ming Shao§, and Xiao-Ming Yin, Supported in part by the NIH funds (CA83817, CA111456 and NS45252). A recipient of the Overseas Young Scholar Award of Natural Science Foundation of China{ddagger}2

From the Departments of {ddagger}Pathology and Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pennsylvania 15261 and the §Department of Surgery, Cancer Hospital, Fudan University, Shanghai 200032, China

Autophagy is a cellular response to adverse environment and stress, but its significance in cell survival is not always clear. Here we show that autophagy could be induced in the mammalian cells by chemicals, such as A23187 [GenBank] , tunicamycin, thapsigargin, and brefeldin A, that cause endoplasmic reticulum stress. Endoplasmic reticulum stress-induced autophagy is important for clearing polyubiquitinated protein aggregates and for reducing cellular vacuolization in HCT116 colon cancer cells and DU145 prostate cancer cells, thus mitigating endoplasmic reticulum stress and protecting against cell death. In contrast, autophagy induced by the same chemicals does not confer protection in a normal human colon cell line and in the non-transformed murine embryonic fibroblasts but rather contributes to cell death. Thus the impact of autophagy on cell survival during endoplasmic reticulum stress is likely contingent on the status of cells, which could be explored for tumor-specific therapy.


Received for publication, September 29, 2006 , and in revised form, November 28, 2006.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 A recipient of the American Liver Foundation/Alpha-1 Foundation Scholar Award.

2 To whom correspondence should be addressed: Dept. of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace St., Pittsburgh, PA 15231. Tel.: 412-648-8436; Fax: 412-648-9564; E-mail: xmyin{at}pitt.edu.


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