Beyond the endoplasmic reticulum

Atypical GRP78 in cell viability, signalling and therapeutic targeting

Min Ni, Yi Zhang, Amy S. Lee

Research output: Contribution to journalArticle

265 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)181-188
Number of pages8
JournalBiochemical Journal
Volume434
Issue number2
DOIs
StatePublished - Mar 1 2011

Fingerprint

Cell signaling
Endoplasmic Reticulum
Cell Survival
Tumors
Therapeutics
Cells
Neoplasms
Protein folding
molecular chaperone GRP78
Apoptosis Regulatory Proteins
Mitochondria
Endoplasmic Reticulum Stress
1-Phosphatidylinositol 4-Kinase
Protein Folding
Phosphatidylinositols
Quality Control
Quality control
Membrane Proteins
Leukemia
Homeostasis

Keywords

  • Cell surface
  • Cytosol
  • Endoplasmic reticulum
  • Glucose-regulated protein of 78 kDA (GRP78)
  • Mitochondrion
  • Nucleus

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Beyond the endoplasmic reticulum : Atypical GRP78 in cell viability, signalling and therapeutic targeting. / Ni, Min; Zhang, Yi; Lee, Amy S.

In: Biochemical Journal, Vol. 434, No. 2, 01.03.2011, p. 181-188.

Research output: Contribution to journalArticle

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