Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5589575 | Gene | 2017 | 25 Pages |
Abstract
The HSPA5 gene encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca2+ homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane. When unfolded/misfolded proteins in the ER overwhelm the capacity of protein folding machinery, BiP can initiate the unfolded protein response (UPR), decrease unfolded/misfolded protein load, induce autophagy, and crosstalk with apoptosis machinery to assist in the cell survival decision. Post-translational modifications (PTMs) of BiP have been shown to regulate BiP's activity, turnover, and availability upon different extrinsic or intrinsic stimuli. As a master regulator of ER function, BiP is associated with cancer, cardiovascular disease, neurodegenerative disease, and immunological diseases. BiP has been targeted in cancer therapies and shows promise for application in other relevant diseases.
Keywords
protein kinase-like ER kinaseeIF2αATF6IP3R3HLA-DRGRP78MHC-ICD86MPP +NBD 1-methyl-4-phenylpyridiniumcluster of differentiation 86VCPKDELDerlin-1Th1/2sec61EDEM1Sig-1RLys-Asp-Glu-LeuGPx7mitochondria-associated ER membraneTCRαGPiMAMSBDERADPTMUPRPI3KIRE1BiPMAPKamino acidinositol-requiring enzyme 1post-translational modificationinterleukinBIKER-Associated Degradationtumor necrosis factor alphaCHOPApoptosissubstrate-binding domainnucleotide-binding domaineukaryotic initiation factor 2 alphaTNF-αphosphoinositide 3-kinaseactivating transcription factor 6Drug targetCalcium homeostasisUnfolded protein responseUnfolded protein response (UPR)Binding immunoglobulin Protein78 kDa glucose-regulated proteinValosin-containing proteinCCAAT-enhancer-binding protein homologous proteinmitogen-activated protein kinasePERKglycosylphosphatidylinositol
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Authors
Jie Wang, Jessica Lee, David Liem, Peipei Ping,