Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated, cDNA cloned and characterised a 29-kDa protein (ERp29), containing a C-terminal endoplasmic reticulum(ER)-retrieval signal, from the rat liver ER. ERp29 was induced to high levels in the rat hepatoma cells under metabolic stress conditions known to cause an aberrant accumulation of proteins in the ER [(e.g. culture in presence of the Ca2+ ionophore A23187, inhibitors of Ca2+-ATPase (thapsigargin), intracellular protein transport (brefeldin A), or protein N-glycosylation (tunicamycin)]. Experimental evidence of its localisation in the luminal compartment of the ER was obtained by topology studies including immunofluorescence microscopy, in vitro translation and proteinase protection assay. ERp29 constitutes about 0.1% of the rat hepatic microsomal proteins and is constitutively expressed in all rat tissues examined, as evident from northern blot analysis. In rat hepatoma cells ERp29 was found to be associated with the abundant molecular chaperone/stress protein BiP/GRP78 and this interaction was significantly enhanced after treatment with tunicamycin and A23187. Taken together, these results suggest that ERp29 is a member of the stress-response machinery of the ER.
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PMID:A stress-inducible rat liver endoplasmic reticulum protein, ERp29. 949 98

ERp29, a novel and ubiquitously expressed endoplasmic reticulum (ER) stress-inducible protein, was recently isolated and cDNA cloned in our laboratory. Using size exclusion chromatography and chemical cross-linking we have assessed the oligomerization properties of ERp29. Purified ERp29 in solution as well as in rat hepatoma cells self-associates predominantly into homodimers. Labeling of the cells with [35S]methionine with subsequent cross-linking and immunoprecipitation showed that ERp29 interacts with a number of ER proteins, one of which was previously identified as BiP/GRP78. Secondary structure prediction and fold recognition methods indicate that the native conformation of ERp29 resembles the thioredoxin fold, a structural motif characteristic of a number of enzymes with the redox function, including protein disulfide isomerase (with which ERp29 shares limited sequence similarity). Dimerization of the protein is suggested to be advantageous for the protein binding potential of ERp29.
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PMID:Oligomerization properties of ERp29, an endoplasmic reticulum stress protein. 971 35

Folding and post-translational modification of the thyroid hormone precursor, thyroglobulin (Tg), in the endoplasmic reticulum (ER) of the thyroid epithelial cells is facilitated by several molecular chaperones and folding enzymes, such as BiP, GRP94, calnexin, protein disulfide isomerase, ERp72, and others. They have been shown to associate simultaneously and/or sequentially with Tg in the course of its maturation, thus forming large heterocomplexes in the ER of thyrocytes. Here we present evidence that such complexes include a novel member, an ER-resident lumenal protein, ERp29, which is present in all mammalian tissues with exceptionally high levels of expression in the secretory cells. ERp29 was induced upon treatment of FRTL-5 rat thyrocytes with the thyroid-stimulating hormone, which is essential for the maintenance of thyroid cells and Tg biosynthesis. Chemical cross-linking followed by the cell lysis and immunoprecipitation of ERp29 or Tg revealed association of these proteins and additionally, immunocomplexes that also included major ER chaperones, BiP and GRP94. Sucrose density gradient analysis indicated co-localization of ERp29 with Tg and BiP in the fractions containing large macromolecular complexes. This was supported by immunofluorescent microscopy showing co-localization of ERp29 with Tg in the putative transport vesicular structures. Affinity chromatography using Tg as an affinity ligand demonstrated that ERp29 might be selectively isolated from the FRTL-5 cell lysate or purified lumenal fraction of rat liver microsomes along with the other ER chaperones. Preferential association with the urea-denatured Tg-Sepharose was indicative of either direct or circuitous ERp29/Tg interactions in a chaperone-like manner. Despite the presence of the C-terminal ER-retrieval signal, significant amounts of ERp29 were also recovered from the culture medium of stimulated thyrocytes, indicating ERp29 secretion. Based on these data, we suggest that the function of ERp29 in thyroid cells is connected with folding and/or secretion of Tg.
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PMID:Identification of ERp29, an endoplasmic reticulum lumenal protein, as a new member of the thyroglobulin folding complex. 1188 2

ERp29 is a recently discovered resident of the endoplasmic reticulum (ER) that is abundant in brain and most other mammalian tissues. Investigations of nonneural secretory tissues have implicated ERp29 in a major role producing export proteins, but a molecular activity remains wanting for this functional orphan. Intriguingly, ERp29 appears to be heavily utilized in the cerebellum, a brain region not conventionally regarded as neurosecretory. To elucidate this functional quandary, we used immunochemical approaches to characterize the regional, cellular, and subcellular distributions of ERp29 in rat brain. Immunohistochemistry revealed ubiquitous expression in neuronal and nonneuronal cells, with a distinctive variation in somatic ERp29 levels. Highly expressing cells were found in diverse locations, implying that ERp29 is not biased towards the cerebellum functionally. Using immunolocalization data mined from the literature, a proteomic profile was developed to assess the functional significance of ERp29's characteristic expression pattern. Surprisingly, ERp29 correlated poorly with classical markers of neurosecretion, but strongly with a variety of major membrane proteins. Together with immunogold localization of ERp29 to somatic ER, these observations led to a novel hypothesis that ERp29 is involved primarily in production of endomembrane proteins rather than proteins destined for export. This study establishes ERp29 as a general ER marker for brain cells and provides a stimulating clue about ERp29's enigmatic function. ERp29 appears to have broad significance for neural pathophysiology, given its ubiquitous distribution and prominence in brain over classical ER residents like BiP and protein disulfide isomerase.
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PMID:ERp29, a general endoplasmic reticulum marker, is highly expressed throughout the brain. 1528 Oct 78

Recent studies have begun to focus on the signals that regulate axonal protein synthesis and the functional significance of localized protein synthesis. However, identification of proteins that are synthesized in mammalian axons has been mainly based on predictions. Here, we used axons purified from cultures of injury-conditioned adult dorsal root ganglion (DRG) neurons and proteomics methodology to identify axonally synthesized proteins. Reverse transcription (RT)-PCR from axonal preparations was used to confirm that the mRNA for each identified protein extended into the DRG axons. Proteins and the encoding mRNAs for the cytoskeletal proteins beta-actin, peripherin, vimentin, gamma-tropomyosin 3, and cofilin 1 were present in the axonal preparations. In addition to the cytoskeletal elements, several heat shock proteins (HSP27, HSP60, HSP70, grp75, alphaB crystallin), resident endoplasmic reticulum (ER) proteins (calreticulin, grp78/BiP, ERp29), proteins associated with neurodegenerative diseases (ubiquitin C-terminal hydrolase L1, rat ortholog of human DJ-1/Park7, gamma-synuclein, superoxide dismutase 1), anti-oxidant proteins (peroxiredoxins 1 and 6), and metabolic proteins (e.g., phosphoglycerate kinase 1 (PGK 1), alpha enolase, aldolase C/Zebrin II) were included among the axonally synthesized proteins. Detection of the mRNAs encoding each of the axonally synthesized proteins identified by mass spectrometry in the axonal compartment indicates that the DRG axons have the potential to synthesize a complex population of proteins. Local treatment of the DRG axons with NGF or BDNF increased levels of cytoskeletal mRNAs into the axonal compartment by twofold to fivefold but had no effect on levels of the other axonal mRNAs studied. Neurotrophins selectively increased transport of beta-actin, peripherin, and vimentin mRNAs from the cell body into the axons rather than changing transcription or mRNA survival in the axonal compartment.
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PMID:Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. 1567 57

It was previously reported that the up-regulation of ERp29 mRNA depends on the levels of thyroid stimulating hormone (TSH) in the thyrocytes of FRTL-5 cells. In order to investigate the putative new function of ERp29 as an endoplasmic molecular (ER) chaperone, an ERp29-overexpressing FRTL-5 cell line was established. This cell line had approximately three times the levels of ERp29 protein and an enhanced level of thyroglobulin (Tg) secretion. The results showed both enhanced ERp29 expression and an interaction with the other ER chaperones such as GRP94, BiP, ERp72 and calnexin. In addition, ERp29 enhanced the expression of PKR-like ER kinase (PERK), which is a transmembrane protein located in the ER membrane. These findings suggest that ERp29 assists in protein folding as well as in the secretion of the secretory/plasma membrane proteins under close co-operation with other ER chaperones and the ER stress signaler, PERK.
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PMID:Overexpression of ERp29 in the thyrocytes of FRTL-5 cells. 1586 5

The biomedical need for streamlined approaches to monitor proteome dynamics is growing rapidly. This study examined the ability of a knowledge-based triplex-profiling strategy (i.e., three functionally distinct chaperones, ERp29/PDI/BiP) to clarify uncertainties about how cancer affects the endoplasmic reticulum (ER) proteome. Investigating a wide range of samples at the tissue and cellular levels (>114 samples from 9 tissues of origin), we obtained consistent evidence that the ER proteome undergoes a major but variable expansion in cancer. Three factors having a strong influence on the ER proteome were identified (cancer-cell type, growth rate, culture mode), and the functionally enigmatic chaperone ERp29 was linked distinctively to histogenetic aspects of tumorigenesis. These findings justify pursuit of the ER-proteome as a medical target in cancer, validate ERp29/PDI/BiP profiling as a streamlined yet powerful measure of ER-proteome dynamics, and suggest that biomarker sets based on distinct functionalities could have broader biomedical utility.
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PMID:Triplex profiling of functionally distinct chaperones (ERp29/PDI/BiP) reveals marked heterogeneity of the endoplasmic reticulum proteome in cancer. 1859 68

We demonstrated that up-regulation of gene expression of endoplasmic reticulum (ER) chaperones (BiP, calnexin, calreticulin, ERp29) and ER membrane kinases (IRE1, PERK, ATF6) was induced by radiation in neuronal PC12 cells. However, addition of silkworm, Bombyx mori, hemolymph to irradiated cells resulted in an obvious decrease in expression of these genes, compared with a single radiation treatment. In contrast, one of the ER chaperones, "ischemia-responsive protein 94 kDa" (irp94), was up-regulated by radiation. However, addition of silkworm hemolymph resulted in no change in the expression of irp94, with an expression pattern that differed from that of ER chaperones. Based on these results, we propose that silkworm hemolymph contains factors that regulate a decrease in the expression of ER chaperones under radiation-irradiation conditions, with the exception of irp94, which is not down-regulated. We suggest that this difference in the molecular character of irp94 may provide a clue to the biological functions associated with ER stress pathways, particularly the effects of radiation.
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PMID:Silkworm hemolymph down-regulates the expression of endoplasmic reticulum chaperones under radiation-irradiation. 2184 89