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Gene. 2017 Jun 30;618:14-23. doi: 10.1016/j.gene.2017.03.005. Epub 2017 Mar 7.

HSPA5 Gene encoding Hsp70 chaperone BiP in the endoplasmic reticulum.

Author information

1
Departments of Physiology, Medicine (Cardiology) and Bioinformatics, NIH BD2K Center of Excellence for Biomedical Computing, University of California Los Angeles, Los Angeles, CA 90095, USA.
2
Departments of Physiology, Medicine (Cardiology) and Bioinformatics, NIH BD2K Center of Excellence for Biomedical Computing, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: peipeiping@earthlink.net.

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:

Apoptosis; Calcium homeostasis; Drug target; ER-associated protein degradation (ERAD); Post-translational modification; Unfolded protein response (UPR)

PMID:
28286085
PMCID:
PMC5632570
DOI:
10.1016/j.gene.2017.03.005
[Indexed for MEDLINE]
Free PMC Article

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