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)

The stress-induced unfolded protein response (UPR) is the only signaling pathway known to regulate expression of genes encoding the resident endoplasmic reticulum (ER) molecular chaperones and folding enzymes, yet these genes are constitutively expressed in all cells. We have examined the expression of ER chaperones in several cell lines that are dependent on a variety of cytokines for growth and survival. When the various cell lines were deprived of essential growth factors, mRNA levels of the ER chaperones BiP and GRP94 decreased dramatically. Re-stimulation of ligand-deprived cells with the appropriate growth factor induced BiP and GRP94 as delayed-early response genes. Cytokine induction of BiP and GRP94 biosynthesis was not preceded by a burst of glycoprotein traffic through the ER nor accompanied by expression of the CHOP transcription factor. The glycosylation inhibitor tunicamycin potently induced expression of both ER chaperones and CHOP in ligand-deprived cells, demonstrating that the UPR pathway remains functionally intact in the absence of growth factor-mediated signaling. Therefore, basal expression of ER chaperones is dependent upon and regulated by a mitogenic pathway distinct from the stress-inducible UPR cascade and this probably controls expression of ER chaperones and folding enzymes needed to assist protein biogenesis in the ER of normal, non-stressed cells.
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PMID:A pathway distinct from the mammalian unfolded protein response regulates expression of endoplasmic reticulum chaperones in non-stressed cells. 938 97

Glucose-regulated protein 58 (GRP58/ER-60/ERp57), best known as a chaperone in the endoplasmic reticulum lumen, was previously identified by us as one of several accessory proteins in the S100 cytosol fraction of human hepatoma Hep3B cells that was differentially coshifted by anti-Stat3 antibody in an antibody-subtracted differential protein display assay. In the present study, the association between GRP58 and Stat3 in different cytoplasmic compartments was evaluated using cross-immunoprecipitation and cell-fractionation techniques. In the S100 cytosol fraction, three different anti-GRP58 polyclonal antibodies (pAb) cross-immunoprecipitated Stat3 (but not Stat1), and, conversely, anti-Stat3 pAb cross-immunoprecipitated GRP58. Both cytosolic Stat3 and GRP58 eluted during Superose-6 gel-filtration chromatography in complexes of size 200-400 kDa (statosome I), and anti-Stat3 pAb cross-immunoprecipitated GRp58 from these FPLC elution fractions. Using differential sedimentation and density equilibrium flotation methods, Stat3 and GRP58 were observed to be coassociated with cytoplasmic membranes enriched for the plasma membrane marker 5' nucleotidase but not with those containing the endoplasmic reticulum marker BiP/GRP78. The Stat3 and GRP58-containing plasma membrane fraction also contained Stat1, Stat5b, and gp130. Stat activation by orthovanadate caused the accumulation of PY-Stat3 in the GRP58-containing plasma membrane fraction. However, this PY-Stat3 was DNA-binding deficient. Likewise, excess exogenous recombinant human GRP58 prepared using a baculovirus expression system preferentially inhibited Stat3 DNA-binding activity in the S100 cytosol, suggesting that GRP58 may sequester activated Stat3. The new data confirm the association between GRP58 and Stat3 in cytosolic 200-400-kDa statosome I complexes and show that both GRP58 and Stat family members coassociate in the plasma membrane compartment. We suggest that the chaperone GRP58 may regulate signaling by sequestering inactive and activated Stat3.
J Interferon Cytokine Res 2002 May
PMID:Association of the chaperone glucose-regulated protein 58 (GRP58/ER-60/ERp57) with Stat3 in cytosol and plasma membrane complexes. 1206 Apr 94

Human myxovirus resistance gene A (MxA) is a type I interferon-inducible protein and exhibits the antiviral activity against a variety of RNA viruses, including influenza virus. Previously, we reported that MxA accelerates cell death of influenza virus-infected cells through caspase-dependent and -independent mechanisms. Similar to other viruses, influenza virus infection induces endoplasmic reticulum (ER) stress, which is one of cell death inducers. Here, we have demonstrated that MxA enhances ER stress signaling in cells infected with influenza virus. ER stress-induced events, such as expression of BiP mRNA and processing of XBP1 mRNA, were upregulated in cells expressing MxA by treatment with an ER stress inducer, tunicamycin (TM), as well as influenza virus infection. TM-induced cell death was also accelerated by MxA. Furthermore, we showed that MxA interacts with BiP and overexpression of BiP reduces MxA-promoted ER stress signaling. Because cell death in virus-infected cells is one of ultimate anti-virus mechanisms, we propose that MxA-enhanced ER stress signaling is a part of the antiviral activity of MxA by accelerating cell death.
J Interferon Cytokine Res 2011 Nov
PMID:Interferon-inducible antiviral protein MxA enhances cell death triggered by endoplasmic reticulum stress. 2199 52