GRP78 (glucose-regulated protein of 78 kDa) is traditionally regarded as a major ER (endoplasmic reticulum) chaperone facilitating protein folding and assembly, protein quality control, Ca2+ binding and regulating ER stress signalling. It is a potent anti-apoptotic protein and plays a critical role in tumour cell survival, tumour progression and angiogenesis, metastasis and resistance to therapy. Recent evidence shows that GRP78 can also exist outside the ER. The finding that GRP78 is present on the surface of cancer but not normal cells in vivo represents a paradigm shift on how GRP78 controls cell homoeostasis and provides an opportunity for cancer-specific targeting. Cell-surface GRP78 has emerged as an important regulator of tumour cell signalling and viability as it forms complexes with a rapidly expanding repertoire of cell-surface protein partners, regulating proliferation, PI3K (phosphoinositide 3-kinase)/Akt signalling and cell viability. Evidence is also emerging that GRP78 serves as a receptor for viral entry into host cells. Additionally, a novel cytosolic form of GRP78 has been discovered prominently in leukaemia cells. These, coupled with reports of nucleus- and mitochondria-localized forms of GRP78, point to the previously unanticipated role of GRP78 beyond the ER that may be critical for cell viability and therapeutic targeting.
Skip Nav Destination
Article navigation
March 2011
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Review Article|
February 11 2011
Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting
Min Ni;
1Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, USC Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, U.S.A.
Search for other works by this author on:
Yi Zhang;
Yi Zhang
1
1Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, USC Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, U.S.A.
Search for other works by this author on:
Amy S. Lee
Amy S. Lee
3
1Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, USC Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, U.S.A.
3To whom correspondence should be addressed (email amylee@ccnt.usc.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 24 2010
Revision Received:
November 12 2010
Accepted:
November 16 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 434 (2): 181–188.
Article history
Received:
September 24 2010
Revision Received:
November 12 2010
Accepted:
November 16 2010
Citation
Min Ni, Yi Zhang, Amy S. Lee; Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochem J 1 March 2011; 434 (2): 181–188. doi: https://doi.org/10.1042/BJ20101569
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.