Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders.
GRP78/BiP is a major endoplasmic reticulum (ER) chaperone protein critical for protein quality control of the ER, as well as controlling the activation of the ER-transmembrane signaling molecules. Through creation of mouse models targeting the Grp78 allele, the function of GRP78 in development and disease has been investigated. These led to the discovery that GRP78 function is obligatory for early embryonic development. However, in adult animals, GRP78 is preferably required for cancer cell survival under pathologic conditions such as tumor progression and drug resistance. The discovery of surface localization of GRP78 in cancer cells reveals potential novel function, interaction with cell-surface receptors, and possible therapeutic implications. Mouse models also reveal that GRP78 controls maturation and secretion of neuronal factors for proper neural migration and offers neuroprotection.
Wang
Miao
M
Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, USC/Norris Comprehensive Cancer Center, Los Angeles, California 90089-9176, USA.
Wey
Shiuan
S
Zhang
Yi
Y
Ye
Risheng
R
Lee
Amy S
AS
D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology*; D009422:Nervous System Diseases / Q000503:physiopathology*; D017510:Protein Folding
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse