The critical role of GRP78 in physiologic and pathologic stress

被引:271
作者
Pfaffenbach, Kyle T. [1 ]
Lee, Amy S. [1 ]
机构
[1] Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA
基金
美国国家卫生研究院;
关键词
ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; PROSTATE-CANCER CELLS; BOX-BINDING PROTEIN-1; COOH-TERMINAL DOMAIN; ER STRESS; CHAPERONE GRP78/BIP; REGULATOR GRP78/BIP; SURFACE GRP78; HEPATIC STEATOSIS;
D O I
10.1016/j.ceb.2010.09.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
GRP78 is a major endoplasmic reticulum chaperone as well as a master regulator of the unfolded protein response. In addition to playing an essential role in early embryonic development, recent studies have emerged specifically implicating GRP78 and chaperone integrity in the aging process and age-related diseases. Another exciting discovery is the regulation of GRP78 by insulin/IGF-1 signaling pathways impacting cell proliferation and survival. Mouse models of cancer, in combination with cell culture studies, validate the critical role of GRP78 in tumorigenesis and tumor angiogenesis. Further, these studies demonstrate the ability of GRP78 to suppress oncogenic PI3K/AKT signaling. The discovery of cell surface GRP78, in cancer cells and cells undergoing ER stress, presents a novel therapeutic strategy.
引用
收藏
页码:150 / 156
页数:7
相关论文
共 53 条
[41]   The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas [J].
Pyrko, Peter ;
Schoenthal, Axel H. ;
Hofman, Florence M. ;
Chen, Thomas C. ;
Lee, Amy S. .
CANCER RESEARCH, 2007, 67 (20) :9809-9816
[42]   Carbonylation of ER chaperone proteins in aged mouse liver [J].
Rabek, JP ;
Boylston, WH ;
Papaconstantinou, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 305 (03) :566-572
[43]   A trip to the ER: coping with stress [J].
Rutkowski, DT ;
Kaufman, RJ .
TRENDS IN CELL BIOLOGY, 2004, 14 (01) :20-28
[44]   GRP78 and cripto form a complex at the cell surface and collaborate to inhibit transforming growth factor β signaling and enhance cell growth [J].
Shani, Gidi ;
Fischer, Wolfgang H. ;
Justice, Nicholas J. ;
Kelber, Jonathan A. ;
Vale, Wylie ;
Gray, Peter C. .
MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (02) :666-677
[45]   Stress chaperone GRP78/BiP confers chemoresistance to tumor-associated endothelial cells [J].
Virrey, Jenilyn J. ;
Dong, Dezheng ;
Stiles, Caryn ;
Patterson, John B. ;
Pen, Ligaya ;
Ni, Min ;
Schoenthal, Axel H. ;
Chen, Thomas C. ;
Hofman, Florence M. ;
Lee, Amy S. .
MOLECULAR CANCER RESEARCH, 2008, 6 (08) :1268-1275
[46]  
Wang M, 2009, ANTIOXID REDOX SIGN, V11, P2307, DOI [10.1089/ars.2009.2485, 10.1089/ARS.2009.2485]
[47]   A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response [J].
Winnay, Jonathon N. ;
Boucher, Jeremie ;
Mori, Marcelo A. ;
Ueki, Kohjiro ;
Kahn, C. Ronald .
NATURE MEDICINE, 2010, 16 (04) :438-U120
[48]   From acute ER stress to physiological roles of the Unfolded Protein Response [J].
Wu, J ;
Kaufman, RJ .
CELL DEATH AND DIFFERENTIATION, 2006, 13 (03) :374-384
[49]   A Phos-Tag-Based Approach Reveals the Extent of Physiological Endoplasmic Reticulum Stress [J].
Yang, Liu ;
Xue, Zhen ;
He, Yin ;
Sun, Shengyi ;
Chen, Hui ;
Qi, Ling .
PLOS ONE, 2010, 5 (07)
[50]  
YE R, 2010, AM J PATHOL IN PRESS