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)

A procedure was developed for the isolation of reticuloplasm, the luminal material of the endoplasmic reticulum (ER). A reticuloplasm-rich extract was prepared from a murine plasmacytoma cell line that contains large amounts of ER, by first extracting the cytoplasmic contents using hypotonic lysis to yield ER-rich 'shells' followed by mechanical lysis to release the ER contents. The extract contains five major proteins with apparent molecular weights of 100, 75, 60, 58 and 55 (X 10(3] Mr by SDS-polyacrylamide gel electrophoresis. The 100, 75 and 58 (X 10(3] Mr species were identified as the known ER proteins endoplasmin, BiP and PD1, respectively. The ER association of the 60 and 55 (X 10(3] Mr proteins was confirmed by confocal fluorescence microscopy with affinity-purified antibodies. Equilibrium dialysis with isolated reticuloplasm gave a calcium-binding capacity of 300 nmoles calcium per mg protein with half-maximal binding at 3 mM-Ca2+. Purified endoplasmin bound 280 nmoles calcium per mg protein at a calcium concentration of 5 mM-Ca2+. A calcium overlay test revealed that, in addition to endoplasmin, reticuloplasm contained at least three other calcium-binding proteins: i.e. BiP, PDI and the 55 X 10(3) Mr protein, respectively, with endoplasmin and the 55 X 10(3) Mr protein (CRP55) accounting for the major proportion of the calcium-binding activity. Treatment of cells with calcium ionophore led to the specific over-expression of the major calcium-binding reticuloplasmins endoplasmin, BiP and CRP55. These studies show that the lumen of the ER contains a family of proteins with the capacity to bind significant amounts of calcium in the millimolar range and thereby to confer upon the ER the ability to perform a calcium storage function analogous to that of the sarcoplasmic reticulum in muscle cells.
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PMID:Identification of a set of calcium-binding proteins in reticuloplasm, the luminal content of the endoplasmic reticulum. 325 4

Two pathways operate to target newly-synthesised proteins to the endoplasmic reticulum. In one, the signal recognition particle attaches to the signal sequences of nascent chains on ribosomes and slows or stops translation until contact is made with the docking protein at the membrane. The second operates via molecular chaperons. The pathways converge at the level of a 43 kDa signal binding protein integrated into the membrane, where translocation through a proteinaceous pore is initiated. In the lumen, proteins fold and disulphide formation is catalysed by the enzyme protein disulphide isomerase. The heavy chain binding protein may attach to unassembled or unfolded proteins and prevent their exit from the ER to the Golgi. Cholecystokinin (CCK) treatment increases the biosynthesis and secretion of pancreatic proteins, increases the levels of PDI and the 43 kDa binding protein, and reduces levels of BiP. These proteins may be possible targets for genetic manipulation to improve processing of heterologous proteins from cultured mammalian cells.
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PMID:Changes in levels of pancreatic endoplasmic reticulum proteins that function in translocation and maturation of secretory proteins in response to cholecystokinin. 776 25

PDI catalyzes the formation of disulfide bonds and plays a central role in the correct folding of nascent polypeptides. In addition, it is multifunctional and may participate in more complex enzyme systems, catalyzing other protein modification. PDI is also known to bind T3. The human T3BP/PDI gene, located in the chromosome 17, consists of a transcribed part of 16.5 kb and the protein coding sequence is divided into 11 exons. The analysis of the 5'-flanking region revealed several putative transcriptional elements, including a TATA box, 6 CCAAT elements and 5 GC-rich regions, each of which is related to the promoter activity. The mechanism of T3BP/PDI gene expression is, however, unknown. Treatment with T4, PTU, insulin and fasting-refeeding induced different responses in T3BP/PDI mRNA and protein levels among various tissues. Recent studies revealed that the unfolded proteins, accumulated in the ER lumen, might stimulate the gene expression of a set of protein including BiP, GRp94 and PDI, which is required for proper protein folding and assembling. The meaning of T3-binding activity of PDI is open for further study.
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PMID:[Regulation of thyroid hormone binding protein/protein disulfide isomerase (T3BP/PDI) gene expression]. 819 77

The synthesis of gluten proteins in the developing caryopsis of wheat is highly coordinated, with mRNAs for the various groups being detected from 11 days after anthesis, and the proteins from about 14 days. In contrast, the levels of transcripts for BiP, PDI and PPI are highest at earlier stages of development. The levels of transcripts for two small GTP binding proteins involved in the secretory pathway (Rab1 and Rab5) are also highest early in development, which is consistent with the retention of most of the gluten proteins within the ER to form protein bodies.
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PMID:Comparison of the expression patterns of genes coding for wheat gluten proteins and proteins involved in the secretory pathway in developing caryopses of wheat. 863 44

Soybean peribacteroid membrane (PBM) proteins were isolated from nitrogen-fixing root nodules and subjected to N-terminal sequencing. Sequence data from 17 putative PBM proteins were obtained. Six of these proteins are homologous to proteins of known function. These include three chaperones (HSP60, BiP [HSP70], and PDI) and two proteases (a serine and a thiol protease), all of which are involved in some aspect of protein processing in plants. The PBM homologs of these proteins may play roles in protein translocation, folding, maturation, or degradation in symbiosomes. Two proteins are homologous to known, nodule-specific proteins from soybean, nodulin 53b and nodulin 26B. Although the function of these nodulins is unknown, nodulin 53b has independently been shown to be associated with the PBM. All of the eight proteins with identifiable homologs are likely to be peripheral rather than integral membrane proteins. Possible reasons for this apparent bias are discussed. The identification of homologs of HSP70 and HSP60 associated with the PBM is the first evidence that the molecular machinery for co- or post-translational import of cytoplasmic proteins is present in symbiosomes. This has important implications for the biogenesis of this unique, nitrogen-fixing organelle.
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PMID:Identification with proteomics of novel proteins associated with the peribacteroid membrane of soybean root nodules. 1070 58

A general route for protein synthesis in eukaryotic cells has been proposed and applied to monoclonal antibody (MAb) synthesis. It takes into account transcription of the gene, binding of ribosomes to mRNA, and polypeptide elongation including binding to SRP (signal recognition particles) and SRP-receptor, competing translocation, folding and glycosylation, assembly of the heavy and light chains in a tetrameric protein and Golgi processing and secretion. A comprehensive model was built on the basis of the proposed pathway. The model takes into account the mechanism of each step. Metabolic control analysis (MCA) principles were applied to the general pathway using the proposed model, and control coefficients were calculated. The results show a shared flux control (of both pathway flux and flux ratio at the branch) among different steps, i.e., transcription, folding, glycosylation, translocation and building blocks synthesis. The steps sharing the control depend on the concentration of building blocks, pathway flux and levels of OST (oligosacharyl transferase), BiP (heavy chain binding protein) and PDI (protein disulfide isomerase). Model predictions compare well with experimental data for MAb synthesis, explaining the control structure of the route and the heterogeneity of the product and also addressing future targets for improvement of the production rate of MAbs.
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PMID:Metabolic control analysis of monoclonal antibody synthesis. 1131 97

Degradation of proteins that, because of improper or suboptimal processing, are retained in the endoplasmic reticulum (ER) involves retrotranslocation to reach the cytosolic ubiquitin-proteasome machinery. We found that substrates of this pathway, the precursor of human asialoglycoprotein receptor H2a and free heavy chains of murine class I major histocompatibility complex (MHC), accumulate in a novel preGolgi compartment that is adjacent to but not overlapping with the centrosome, the Golgi complex, and the ER-to-Golgi intermediate compartment (ERGIC). On its way to degradation, H2a associated increasingly after synthesis with the ER translocon Sec61. Nevertheless, it remained in the secretory pathway upon proteasomal inhibition, suggesting that its retrotranslocation must be tightly coupled to the degradation process. In the presence of proteasomal inhibitors, the ER chaperones calreticulin and calnexin, but not BiP, PDI, or glycoprotein glucosyltransferase, concentrate in the subcellular region of the novel compartment. The "quality control" compartment is possibly a subcompartment of the ER. It depends on microtubules but is insensitive to brefeldin A. We discuss the possibility that it is also the site for concentration and retrotranslocation of proteins that, like the mutant cystic fibrosis transmembrane conductance regulator, are transported to the cytosol, where they form large aggregates, the "aggresomes."
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PMID:A novel quality control compartment derived from the endoplasmic reticulum. 1140 79

Disruption of the calnexin gene in Saccharomyces cerevisiae did not lead to gross effects on the levels of cell growth and secretion of wild-type hen egg white lysozymes (HEWL). To investigate the function of calnexin in relation to the secretion of glycoproteins, we expressed both stable and unstable mutant glycosylated lysozymes in calnexin-disrupted S. cerevisiae. The secreted amounts of stable mutant glycosylated lysozymes (G49N and S91T/G49N) were almost the same in both wild-type and calnexin-disrupted S. cerevisiae. In contrast, the secretion of unstable mutant glycosylated lysozymes (K13D/G49N, C76A/G49N, and D66H/G49N) greatly increased in calnexin-disrupted S. cerevisiae, although their secretion was very low in the wild-type strain. This indicates that calnexin may act in the quality control of glycoproteins. We further investigated the expression level of the mRNA of the molecular chaperones BiP and PDI, which play a major role in the protein folding process in the ER, when glycosylated lysozymes were expressed in wild-type and calnexin-disrupted S. cerevisiae. The mRNA concentrations of BiP and PDI were evidently increased when the glycosylated lysozymes were expressed in calnexin-disrupted S. cerevisiae. This observation indicates that BiP and PDI may be induced by the accumulation of unfolded glycosylated lysozymes due to the deletion of calnexin.
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PMID:Effects of calnexin deletion in Saccharomyces cerevisiae on the secretion of glycosylated lysozymes. 1172 75

Both glycosylated amyloidogenic lysozymes I55T/G49N and D66H/G49N were expressed in wild-type and calnexin-disrupted Saccharomyces cerevisiae. The secretion amounts of mutant I55T/G49N were almost similar in both wild-type and calnexin-disrupted S. cerevisiae. In contrast, the secretion of mutant D66H/G49N greatly increased in calnexin-disrupted S. cerevisiae, while the secretion was very low in the wild-type strain. In parallel, the induction level of the molecular chaperones BiP and PDI located in the endoplasmic reticulum (ER) was investigated when these glycosylated amyloidogenic lysozymes were expressed in wild-type and calnexin-disrupted S. cerevisiae. The mRNA concentrations of BiP and PDI were evidently increased when mutant lysozyme D66H/G49N was expressed in calnexin-disrupted S. cerevisiae, while they were not so increased when I55T/G49N mutant was expressed. This observation indicates that the conformation of mutant lysozyme D66H/G49N was less stable in the ER, thus leading to the higher-level expression of ER molecular chaperones via the unfolded protein response pathway. This suggests that glycosylated amyloidogenic lysozyme I55T/G49N may have a relatively stable conformation in the ER, thus releasing it from the quality control of calnexin compared with mutant lysozyme D66H/G49N.
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PMID:Different effects of calnexin deletion in Saccharomyces cerevisiae on the secretion of two glycosylated amyloidogenic lysozymes. 1185 82

The symbiosome membrane represents a specialized plant membrane that forms both a structural and a functional interface between the legume plant and its bacterial counterpart. In this study, the symbiosome membrane protein profile from the model system Medicago truncatula and the corresponding bacterium Sinorhizobium meliloti was examined using two-dimensional electrophoresis and microcapillary high-performance liquid chromatography (HPLC) tandem mass spectrometry. The identities of 51 proteins were obtained and these proteins were categorized into functional classes to indicate biochemical roles. Symbiosome membrane proteins include an H(+)-ATPase, ENOD16, ENOD8, nodulin-25, BiP, HSP70, PDI, multifunctional aquaporin, a putative syntaxin, and other proteins of known and unknown identity and function. The majority of the proteins identified were involved with protein destination and storage. These results allow us to understand better the biochemical composition of the symbiosome membrane and thus provide a basis to hypothesize mechanisms of symbiosome membrane formation and function.
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PMID:Biochemical characterization of symbiosome membrane proteins from Medicago truncatula root nodules. 1476 Jun 46


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