Disease relevance of P4hb

• Downregulation of protein disulfide isomerase inhibits infection by the mouse polyomavirus [1].
• When the alpha (II) subunit was expressed together with the human protein disulfide-isomerase/beta subunit in insect cells by baculovirus vectors, an active prolyl 4-hydroxylase was formed, and this protein appeared to be an alpha (II) 2 beta 2 tetramer [2].
• Induction of the Unfolded Protein Response in Familial Amyotrophic Lateral Sclerosis and Association of Protein-disulfide Isomerase with Superoxide Dismutase 1 [3].
• Rabbit antibodies have been prepared against ERp61, ERp59, and ERp49, three protein components of rough endoplasmic reticulum (RER) purified from mineral oil-induced plasmacytoma 315 (MOPC-315) tissue [4].
• The expression of murine protein disulfide isomerase in Escherichia coli [5].

High impact information on P4hb

• Edman degradation of MTPv1 isolated from transfected cells revealed three unique residues; however, recombinant MTP and MTPv1 had an equivalent protein disulfide isomerase association, subcellular localization, triglyceride transfer, phospholipid transfer, response to inhibitors, and ability to support apoB secretion [6].
• Internuclear exchange of an inner nuclear membrane protein (p55) in heterokaryons: in vivo evidence for the interaction of p55 with the nuclear lamina [7].
• When rat/mouse heterokaryons were constructed using an undifferentiated murine embryonal carcinoma (P19), which lacks lamins A and C, no accumulation of p55 in the mouse cell nucleus was observed [7].
• However, P19 nuclei could be rendered competent to accumulate p55 by transfecting the parent cells with human lamin A before cell fusion, supporting the notion that p55 may interact with the nuclear lamina [7].
• After incubation of the detergent-insoluble matrix of these cells with [gamma-32P]ATP, several alkali-resistant phosphoproteins, including a very heavily labelled 55 000 mol. wt. protein ( p55 ), have been detected in LSTRA, reflecting the activity of a protein kinase specific to this cell line [8].

Chemical compound and disease context of P4hb

• Overexpression of protein disulfide isomerase-like protein in a mouse leukemia L1210 cell line selected for resistance to 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, a ribonucleotide reductase inhibitor [9].
• cDNA cloning and baculovirus expression of the human liver endoplasmic reticulum P58: characterization as a protein disulfide isomerase isoform, but not as a protease or a carnitine acyltransferase [10].

Biological context of P4hb

• Infectibility measured by nuclear T antigen expression was reduced commensurately with the degree of PDI downregulation [1].
• Infectibility was restored by transfection with a plasmid expressing PDI but not with a control expressing catalytically inactive enzyme [1].
• Tissue distribution of three members of the murine protein disulfide isomerase (PDI) family [11].
• We detected a single linkage at the telomeric end of chromosome 11, where the Pdi gene itself resides (logarithm of odds score >30.0) [12].
• A genetic analysis was carried out to determine whether there is a causal relationship between elevated Pdi expression and diabetes phenotype in BTBR-ob/ob mice [12].

Anatomical context of P4hb

• Deconvolution microscopy using fluorescently labeled virus and cellular markers showed that virus reaches the endoplasmic reticulum (ER) normally in cells with reduced PDI but subsequently fails to exit the ER [1].
• Early stages of infection by the mouse polyomavirus have been studied using HeLa cells stably expressing small interfering RNA to protein disulfide isomerase (PDI) [1].
• The ER location of the protein in fibroblasts was immunocytochemically confirmed by double staining for ERp61 and another ER-resident protein, PDI or Hsp47 [13].
• A role for sperm surface protein disulfide isomerase activity in gamete fusion: evidence for the participation of ERp57 [14].
• Expression of SOD1 mutants (mSOD1) led to an up-regulation of PDI in motor neuron-like NSC-34 cells but not other cell lines [3].

Associations of P4hb with chemical compounds

• Protein disulfide isomerase (Pdi) is reported to be an insulin-regulated gene whose expression level is increased in the livers of rats with streptozotocin-induced diabetes [12].
• Inhibition of PDI using bacitracin increased aggregate production, even in wild type SOD1 transfectants that do not readily form inclusions, suggesting PDI may protect SOD1 from aggregation [3].
• ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase [15].
• Endogenous substrates of sphingosine-dependent kinases (SDKs) are chaperone proteins: heat shock proteins, glucose-regulated proteins, protein disulfide isomerase, and calreticulin [16].
• RESULTS: Protein expression patterns varied substantially between species and cell types, with five new abundantly expressed proteins identified including, LDH (Ra, Ch), G3PDH (Hu, Ch), pyruvate kinase (Ch), Annexin II (Ch), and protein disulfide isomerase (Ch) [17].

Regulatory relationships of P4hb

• Protein disulfide isomerase suppresses the transcriptional activity of NF-kappaB [18].

Other interactions of P4hb

• Cloning, baculovirus expression, and characterization of a second mouse prolyl 4-hydroxylase alpha-subunit isoform: formation of an alpha 2 beta 2 tetramer with the protein disulfide-isomerase/beta subunit [2].
• Little to no activity was observed for BiP, ERp72, and protein disulfide isomerase [19].
• Here, ERp72, the other member of the protein disulfide-isomerase family containing three CGHC motifs, was isolated from ER of rat and mouse livers through four sequential chromatographies on DEAE-Toyopearl 650, AF-heparin Toyopearl 650M, and TSK gel G3000SW twice [20].
• Comparative proteomic analysis identifies protein disulfide isomerase and peroxiredoxin 1 as new players involved in embryonic interdigital cell death [21].
• The mRNA for GRP75, a mitochondrial chaperone, HSC70, a cytoplasmic chaperone, protein disulfide isomerase, an endoplasmic reticulum chaperone, and C/EBPalpha, a transcription factor, was not regulated [22].

Analytical, diagnostic and therapeutic context of P4hb

• The gene array results were verified by quantitative real-time PCR that showed highly elevated transcript levels of genes involved in unfolded protein response such as ER and cytoplasmic chaperones, oxidoreductases, protein disulfide isomerase (PDI) family, and ER-associated degradation system such as ubiquitin [23].
• A strong correlation emerged between the experimental results on epitope mapping and predictions of potential antigenicity of murine p55 IL-2R [24].
• In particular, an unconjugated HIV1-p24 peptide containing both B- and T-cell epitopes in tandem plus Freund's adjuvant induced a strong antibody response in both mice and rabbits against p24 and its precursor p55 as judged by immunoblotting [25].
• Animals immunized with these gag particles produced high titer antibodies and Western blot analyses showed that anti-gag pr45 rabbit sera react with p17, p24 and p55 gag proteins of HIV-1 [26].

References