scholarly journals Expression of protein disulfide isomerase family members correlates with tumor progression and patient survival in ovarian cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (61) ◽  
pp. 103543-103556 ◽  
Author(s):  
Soma Samanta ◽  
Shuzo Tamura ◽  
Louis Dubeau ◽  
Paulette Mhawech-Fauceglia ◽  
Yohei Miyagi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Protein Disulfide Isomerase ◽  
Patient Survival ◽  
Family Members ◽  
Disulfide Isomerase ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

scholarly journals Functional Relationship between Protein Disulfide Isomerase Family Members during the Oxidative Folding of Human Secretory Proteins

2010 ◽  
Vol 21 (18) ◽  
pp. 3093-3105 ◽  
Author(s):  
Lori A. Rutkevich ◽  
Myrna F. Cohen-Doyle ◽  
Ulf Brockmeier ◽  
David B. Williams
Keyword(s):  
Protein Disulfide Isomerase ◽  
High Efficiency ◽  
Family Members ◽  
Secretory Proteins ◽  
Human Hepatoma Cells ◽  
Oxidative Folding ◽  
Disulfide Isomerase ◽  
The Impact ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

To examine the relationship between protein disulfide isomerase family members within the mammalian endoplasmic reticulum, PDI, ERp57, ERp72, and P5 were depleted with high efficiency in human hepatoma cells, either singly or in combination. The impact was assessed on the oxidative folding of several well-characterized secretory proteins. We show that PDI plays a predominant role in oxidative folding because its depletion delayed disulfide formation in all secretory proteins tested. However, the phenotype was surprisingly modest suggesting that other family members are able to compensate for PDI depletion, albeit with reduced efficacy. ERp57 also exhibited broad specificity, overlapping with that of PDI, but with preference for glycosylated substrates. Depletion of both PDI and ERp57 revealed that some substrates require both enzymes for optimal folding and, furthermore, led to generalized protein misfolding, impaired export from the ER, and degradation. In contrast, depletion of ERp72 or P5, either alone or in combination with PDI or ERp57 had minimal impact, revealing a narrow substrate specificity for ERp72 and no detectable role for P5 in oxidative protein folding.

scholarly journals Structure-Function Analysis of the Endoplasmic Reticulum Oxidoreductase TMX3 Reveals Interdomain Stabilization of the N-terminal Redox-active Domain

2007 ◽  
Vol 282 (46) ◽  
pp. 33859-33867 ◽  
Author(s):  
Johannes Haugstetter ◽  
Michael Andreas Maurer ◽  
Thomas Blicher ◽  
Martin Pagac ◽  
Gerhard Wider ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Disulfide Isomerase ◽  
Function Analysis ◽  
Transmembrane Protein ◽  
Reduced Form ◽  
Disulfide Isomerase ◽  
Binding Domains ◽  
Redox Active ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

Disulfide bond formation in the endoplasmic reticulum is catalyzed by enzymes of the protein disulfide-isomerase family that harbor one or more thioredoxin-like domains. We recently discovered the transmembrane protein TMX3, a thiol-disulfide oxidoreductase of the protein disulfide-isomerase family. Here, we show that the endoplasmic reticulum-luminal region of TMX3 contains three thioredoxin-like domains, an N-terminal redox-active domain (named a) followed by two enzymatically inactive domains (b and b′). Using the recombinantly expressed TMX3 domain constructs a, ab, and abb′, we compared structural stability and enzymatic properties. By structural and biophysical methods, we demonstrate that the reduced a domain has features typical of a globular folded domain that is, however, greatly destabilized upon oxidization. Importantly, interdomain stabilization by the b domain renders the a domain more resistant toward chemical denaturation and proteolysis in both the oxidized and reduced form. In combination with molecular modeling studies of TMX3 abb′, the experimental results provide a new understanding of the relationship between the multidomain structure of TMX3 and its function as a redox enzyme. Overall, the data indicate that in addition to their role as substrate and co-factor binding domains, redox-inactive thioredoxin-like domains also function in stabilizing neighboring redox-active domains.

scholarly journals Inhibitors of the protein disulfide isomerase family for the treatment of multiple myeloma

Leukemia ◽  
2018 ◽  
Vol 33 (4) ◽  
pp. 1011-1022 ◽  
Author(s):  
Reeder M. Robinson ◽  
Leticia Reyes ◽  
Ravyn M. Duncan ◽  
Haiyan Bian ◽  
Allen B. Reitz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Protein Disulfide ◽  
Protein Disulfide Isomerase Family

scholarly journals PDI Family Members as Guides for Client Folding and Assembly

2020 ◽  
Vol 21 (24) ◽  
pp. 9351
Author(s):  
Shingo Kanemura ◽  
Motonori Matsusaki ◽  
Kenji Inaba ◽  
Masaki Okumura
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Molecular Chaperones ◽  
Protein Disulfide Isomerase ◽  
Family Members ◽  
Secretory Proteins ◽  
Efficient Production ◽  
Protein Homeostasis ◽  
Disulfide Isomerase ◽  
Protein Disulfide

Complicated and sophisticated protein homeostasis (proteostasis) networks in the endoplasmic reticulum (ER), comprising disulfide catalysts, molecular chaperones, and their regulators, help to maintain cell viability. Newly synthesized proteins inserted into the ER need to fold and assemble into unique native structures to fulfill their physiological functions, and this is assisted by protein disulfide isomerase (PDI) family. Herein, we focus on recent advances in understanding the detailed mechanisms of PDI family members as guides for client folding and assembly to ensure the efficient production of secretory proteins.

Sign in / Sign up

Export Citation Format

Share Document