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)

BiP, a resident endoplasmic reticulum member of the HSP70 family of molecular chaperones, associates transiently with a wide variety of newly synthesized exocytotic proteins. In addition to immunoglobulin heavy and light chains, the first natural substrates identified for BiP, a number of viral polypeptides including the human immunodeficiency virus type 1 envelope glycoprotein gp160 interact with BiP during their passage through the endoplasmic reticulum. We have used a computer algorithm developed to predict BiP-binding sites within protein primary sequences to identify sites within gp160 that might mediate its association with BiP. Analysis of the ability of 22 synthetic heptapeptides corresponding to predicted binding sites to stimulate the ATPase activity of BiP or to compete with an unfolded polypeptide for binding to BiP indicated that about half of them are indeed recognized by the chaperone. All of the confirmed binding sites are localized within conserved regions of gp160, suggesting a conserved role for BiP in the folding of gp160. Information on the characteristics of confirmed BiP-binding peptides gained in this and previous studies has been utilized to improve the predictive power of the BiP Score algorithm and to investigate the differences in peptide binding specificities of HSP70 family members.
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PMID:BiP-binding sequences in HIV gp160. Implications for the binding specificity of bip. 1051 65

BiP, an HSP70 molecular chaperone located in the lumen of the endoplasmic reticulum (ER), binds newly-synthesized proteins as they are translocated into the ER and maintains them in a state competent for subsequent folding and oligomerization. BiP is also an essential component of the translocation machinery, as well as playing a role in retrograde transport across the ER membrane of aberrant proteins destined for degradation by the proteasome. BiP is an abundant protein under all growth conditions, but its synthesis is markedly induced under conditions that lead to the accumulation of unfolded polypeptides in the ER. This attribute provides a marker for disease states that result from misfolding of secretory and transmembrane proteins.
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PMID:Role and regulation of the ER chaperone BiP. 1059 29

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

Heat shock protein-based vaccines have been shown to immunize against cancer and infectious diseases in both prophylactic and therapeutic protocols. So far, four classes of heat shock proteins (HSPs) preparation: gp96, HSP90 (hsp86, hsp84), HSP70 (hsc70, hsp70) and calreticulin have been used successfully. The methods for purifying them individually are now readily available. However, since tumors are not always available in large quantity, a major challenge remains the development of a procedure to simultaneously isolate these HSPs from the same sample. We report here that hsp40, hsp60, hsc70, hsp70, hsp84, hsp86, and gp96 (grp94) but not BiP (grp78) and calreticulin can be separated from a single tumor sample in one step using heparin-agarose chromatography. Interestingly this procedure separates the HSP70 isoforms hsp70 from hsc70, but not the HSP90 isoforms hsp84 and hsp86. The three main immunogenic HSPs, gp96, hsp86/84, and hsc70 can be further isolated to homogeneity using additional purification methods. In addition, we have shown that the interaction of the chaperoned peptides with hsc70 and gp96 is not compromised during heparin chromatography. These observations provide a new method for preparation of multiple HSP-based vaccines, circumventing the sample size limitation, as well as providing the possibility to study how multiple HSPs can synergize in eliciting immunity.
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PMID:Purification of multiple heat shock proteins from a single tumor sample. 1072 57

Cotranslational protein transport into dog pancreas microsomes involves the Sec61p complex plus a luminal heat shock protein 70. Posttranslational protein transport into the yeast endoplasmic reticulum (ER) involves the so-called Sec complex in the membrane, comprising a similar Sec61p subcomplex, the putative signal peptide receptor subcomplex, and the heat shock protein 40-type subunit, Sec63p, plus a luminal heat shock protein 70. Recently, human homologs of yeast proteins Sec62p and Sec63p were discovered. Here we determined the concentrations of these two membrane proteins in dog pancreas microsomes and observed that the canine homologs of yeast proteins Sec62p and Sec63p are abundant proteins, present in almost equimolar concentrations as compared with Sec61alphap monomers. Furthermore, we detected fractions of these two proteins in association with each other as well as with the Sec61p complex. The J domain of the human Sec63p was shown to interact with immunoglobulin heavy chain binding protein. Thus, the membrane of the mammalian ER contains components, known from the posttranslationally operating protein translocase in yeast. We suggest that these components are required for efficient cotranslational protein transport into the mammalian ER as well as for other transport processes.
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PMID:Homologs of the yeast Sec complex subunits Sec62p and Sec63p are abundant proteins in dog pancreas microsomes. 1086 Sep 86

High hydrostatic pressure (HP) has recently been shown to increase cellular heat shock protein 70 (Hsp70) level in a specific way that does not involve transcriptional activation of the gene, but rather the stabilisation of the mRNA for Hsp70. In this study, we investigated whether there are other observable changes caused by HP stress, and compared them with those induced by certain other forms of stressors. A chondrocytic cell line T/C28a4 was exposed to 30 MPa continuous HP, heat shock at 43 degrees C, and increased cytosolic calcium concentration by the addition of sarco-endoplasmic reticulum Ca(2+) ATPase inhibitor thapsigargin (25 nM) or calcium ionophore A23187 (1 microM) in the cultures. The protein synthesis was studied by in vitro metabolic labelling followed by one- and two-dimensional polyacrylamide gel electrophoresis, and mass spectrometry was utilized to confirm the identity of the protein spots on two-dimensional gels. Continuous 30 MPa HP increased remarkably the relative labelling of Hsp70. Labelling of Hsp90 was also increased by 15-20%, although no clear change was evident at the protein level in Western blots. Elevated intracellular Ca(2+) concentration induced by thapsigargin and calcium ionophore A23187 increased mainly the synthesis of glucose-regulated protein 78 (Grp78/BiP), whereas Hsp70 and Hsp90 were decreased by the treatment. Heat shock was the strongest inducer of Hsp70 and Hsp90. This study further confirmed the induction of Hsp70 in chondrocytic cells exposed to high HP, but it also showed that calcium-mediated responses are unlikely to cause the stress response observed in the hydrostatically pressurized cells.
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PMID:Differential regulation of stress proteins by high hydrostatic pressure, heat shock, and unbalanced calcium homeostasis in chondrocytic cells. 1099 52

Sleep and waking differ significantly in terms of behavior, metabolism, and neuronal activity. Recent evidence indicates that sleep and waking also differ with respect to the expression of certain genes. To systematically investigate such changes, we used mRNA differential display and cDNA microarrays to screen approximately 10000 transcripts expressed in the cerebral cortex of rats after 8 h of sleep, spontaneous waking, or sleep deprivation. We found that 44 genes had higher mRNA levels after waking and/or sleep deprivation relative to sleep, while 10 were upregulated after sleep. Known genes that were upregulated in waking and sleep deprivation can be grouped into the following categories: immediate early genes/transcription factors (Arc, CHOP, IER5, NGFI-A, NGFI-B, N-Ras, Stat3), genes related to energy metabolism (glucose type I transporter Glut1, Vgf), growth factors/adhesion molecules (BDNF, TrkB, F3 adhesion molecule), chaperones/heat shock proteins (BiP, ERP72, GRP75, HSP60, HSP70), vesicle- and synapse-related genes (chromogranin C, synaptotagmin IV), neurotransmitter/hormone receptors (adrenergic receptor alpha(1A) and beta(2), GABA(A) receptor beta(3), glutamate NMDA receptor 2A, glutamate AMPA receptor GluR2 and GluR3, nicotinic acetylcholine receptor beta(2), thyroid hormone receptor TRbeta), neurotransmitter transporters (glutamate/aspartate transporter GLAST, Na(+)/Cl(-) transporter NTT4/Rxt1), enzymes (aryl sulfotransferase, c-jun N-terminal kinase 1, serum/glucocorticoid-induced serine/threonine kinase), and a miscellaneous group (calmodulin, cyclin D2, LMO-4, metallothionein 3). Several other genes that were upregulated in waking and all the genes upregulated in sleep, with the exception of the one coding for membrane protein E25, did not match any known sequence. Thus, significant changes in gene expression occur across behavioral states, which are likely to affect basic cellular functions such as RNA and protein synthesis, neural plasticity, neurotransmission, and metabolism.
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PMID:Gene expression in the brain across the sleep-waking cycle. 1110 86

The unfolded protein response (UPR) is a signal transduction pathway induced by a variety of endoplasmic reticulum (ER) stresses and functions to maintain homeostasis of the cellular membrane in eukaryotes. Various ER stresses result in the accumulation of unfolded proteins in the ER, which is sensed by the transmembrane protein kinase/ribonuclease Ire1p that transmits a signal from the ER to the nucleus in Saccharomyces cerevisiae. Here we report that the yeast ER chaperone Kar2p/BiP, a member of the HSP70 family found in the ER, directly regulates the UPR by the interaction with Ire1p. In the absence of ER stress, Kar2p binds the lumenal domain of Ire1p and keeps Ire1p in an inactive unphosphorylated state. Upon exposure of cells to ER stresses, Kar2p is released from Ire1p, resulting in activation of Ire1p and signal transduction to the nucleus. Subsequently, KAR2 mRNA is induced and Kar2p accumulates in the ER in a time-dependent manner, restoring the system to the basal state. This negative autoregulation is similar to the regulation of mammalian cytosolic chaperone Hsp70 via its interaction with heat shock factor 1.
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PMID:Dissociation of Kar2p/BiP from an ER sensory molecule, Ire1p, triggers the unfolded protein response in yeast. 1111 6

HSP70 chaperones mediate protein folding by ATP-dependent interaction with short linear peptide segments that are exposed on unfolded proteins. The mode of action of the Escherichia coli homolog DnaK is representative of all HSP70 chaperones, including the endoplasmic reticulum variant BiP/GRP78. DnaK has been shown to be effective in assisting refolding of a wide variety of prokaryotic and eukaryotic proteins, including the alpha-helical homodimeric secretory cytokine interferon-gamma (IFN-gamma). We screened solid-phase peptide libraries from human and mouse IFN-gamma to identify DnaK-binding sites. Conserved DnaK-binding sites were identified in the N-terminal half of helix B and in the C-terminal half of helix C, both of which are located at the IFN-gamma dimer interface. Soluble peptides derived from helices B and C bound DnaK with high affinity in competition assays. No DnaK-binding sites were found in the loops connecting the alpha-helices. The helix C DnaK-binding site appears to be conserved in most members of the superfamily of interleukin (IL)-10-related cytokines that comprises, apart from IL-10 and IFN-gamma, a series of recently discovered small secretory proteins, including IL-19, IL-20, IL-22/IL-TIF, IL-24/MDA-7 (melanoma differentiation-associated gene), IL-26/AK155, and a number of viral IL-10 homologs. These cytokines belong to a relatively small group of homodimeric proteins with highly interdigitated interfaces that exhibit the strongly hydrophobic character of the interior core of a single-chain folded domain. We propose that binding of DnaK to helix C in the superfamily of IL-10-related cytokines may constitute the hallmark of a novel conserved regulatory mechanism in which HSP70-like chaperones assist in the formation of a hydrophobic dimeric "folding" interface.
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PMID:The conserved helix C region in the superfamily of interferon-gamma /interleukin-10-related cytokines corresponds to a high-affinity binding site for the HSP70 chaperone DnaK. 1197 Sep 58

The binding protein BiP is an endoplasmic reticulum (ER)-resident member of the HSP70 stress-related protein family, which is essential for the constitutive function of the ER. In addition to responding to a variety of environmental stimuli, plant BiP exhibits a tissue-specific regulation. We have isolated two soybean BiP genomic clones, designated gsBiP6 and gsBiP9, and different extensions of their 5' flanking sequences were fused to beta-glucuronidase (GUS) reporter gene and introduced into Nicotiana tabacum by Agrobacterium tumefaciens-mediated transformation. Transgenic plants displayed prominent GUS activity in the vascular bundles of roots and shoots as well as in regions of intense cell division, such as procambial region and apical meristems. Promoter deletion analyses identified two cis-regulatory functional domains that are important for the spatially-regulated activation of BiP expression under normal plant development. While an AT-rich enhancer-like sequence, designated cis-acting regulatory domain 1, CRD1 (-358 to -211, on gsBiP6), activated expression of the BiP minimal promoter in all organs analyzed, BiP promoter activity in meristematic tissues and phloem cells required the presence of a second activating domain, CRD2 (-211 to -80). Apparently, the CRD2 sequence also harbors negative cis-acting elements, because removal of this region caused activation of gsBiP6 promoter in parenchymatic xylem rays. These results suggest that the tissue-specific control of BiP gene expression requires a complex integration of multiple cis-acting regulatory elements on the promoter.
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PMID:Tissue-specific regulation of BiP genes: a cis-acting regulatory domain is required for BiP promoter activity in plant meristems. 1237 6


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