Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 May 21:3:30.
doi: 10.3389/fcell.2015.00030. eCollection 2015.

Novel roles for protein disulphide isomerase in disease states: a double edged sword?

Sonam Parakh  1 , Julie D Atkin  2
Affiliations
Review

Novel roles for protein disulphide isomerase in disease states: a double edged sword?

Sonam Parakh et al. Front Cell Dev Biol. .

Abstract

Protein disulphide isomerase (PDI) is a multifunctional redox chaperone of the endoplasmic reticulum (ER). Since it was first discovered 40 years ago the functions ascribed to PDI have evolved significantly and recent studies have recognized its distinct functions, with adverse as well as protective effects in disease. Furthermore, post translational modifications of PDI abrogate its normal functional roles in specific disease states. This review focusses on recent studies that have identified novel functions for PDI relevant to specific diseases.

Keywords: amyotrophic lateral sclerosis; cancer; neurodegnerative diseases; post-translational modifications; protein chaperones; protein disulfide isomerase family.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Domain structure of PDI. The thioredoxin-like domains are shown in green, representing the catalytically active domains a and a'. The catalytically inactive b domain and b' domains are illustrated in orange and red respectively. The linker region x (shown in white) is responsible for the U shape structure of PDI. The C terminus is illustrated in yellow, followed by an ER retrieval signal, KDEL.
Figure 2
Figure 2
Diagram representing disulphide bond formation in the eukaryotic ER and redox reactions involving PDI. Oxidative folding of PDI leads to disulphide bond formation in native protein substrates. Reduced PDI facilitates isomerization of non-native bonds in protein substrates.
Figure 3
Figure 3
Schematic diagram outlining the dual nature of PDI, focusing on neurodegenerative disorders as an example. Under normal conditions, PDI reduces the load of misfolded proteins either by its chaperone activity or by isomerization of non-native bonds. However, during disease states, loss of the normal protective function of PDI as well as the gain of additional, toxic functions, leads to PDI becoming apoptotic, thus contributing to pathology.
Figure 4
Figure 4
Schematic diagram illustrating possible therapeutic applications to modulate PDI function.
See this image and copyright information in PMC

References

    1. Andreu C. I., Woehlbier U., Torres M., Hetz C. (2012). Protein disulfide isomerases in neurodegeneration: from disease mechanisms to biomedical applications. FEBS Lett. 586: 2826–2834. 10.1016/j.febslet.2012.07.023 - DOI - PubMed
    1. Anelli T., Alessio M., Mezghrani A., Simmen T., Talamo F., Bachi A., et al. . (2002). ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J. 21, 835–844. 10.1093/emboj/21.4.835 - DOI - PMC - PubMed
    1. Appenzeller-Herzog C., Ellgaard L. (2008). The human PDI family: versatility packed into a single fold. Biochim. Biophys. Acta 1783, 535–548. 10.1016/j.bbamcr.2007.11.010 - DOI - PubMed
    1. Ataman-Onal Y., Beaulieu C., Busseret S., Charrier J.-P., Choquet-Kastylevsky G., Rolland D., et al. (2013). Protein disulfide isomerase assay method for the in vitro diagnosis of colorectal cancer. Patents 1–30.
    1. Atkin J. D., Farg M. A., Turner B. J., Tomas D., Lysaght J. A., Cheema S. S., et al. . (2006). Induction of the unfolded protein response in familial amyotrophic lateral sclerosis and association of protein-disulfide isomerase with superoxide dismutase 1. J. Biol. Chem. 281, 30152–30165. 10.1074/jbc.M603393200 - DOI - PubMed