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 KAR2 gene of Saccharomyces cerevisiae codes for an essential chaperone protein (BiP) that is localized in the lumen of the endoplasmic reticulum (ER). The high basal rate of transcription of KAR2 is increased transiently by heat shock: prolonged induction occurs when unfolded proteins accumulate in the ER. Three cis-acting elements in the KAR2 promoter control expression of KAR2: (i) a GC-rich region that contributes to the high level of constitutive expression, (ii) a functional heat shock element (HSE) and (iii) an element (UPR) that is involved in the induction of BiP mRNA by unfolded proteins. By analyzing internal deletion mutants of the KAR2 promoter, we demonstrate here that these three elements regulate transcription of KAR2 independently. Furthermore, the 22 bp UPR element causes a heterologous (CYC1) promoter to respond to the presence of unfolded proteins in the ER. Extracts of both stressed and unstressed yeast cells contain proteins that bind specifically to synthetic HSE and UPR elements and retard their migration through gels. Binding proteins specific for the UPR element can be fractionated by ammonium sulfate precipitation. Two of the proteins UPRF-1 and UPRF-2 (which is apparently a proteolytic degradation product of UPRF-1) bind inefficiently to mutant versions of the UPR that are unable to confer responsiveness to unfolded proteins to the (CYC1) promoter. UPRF-1 therefore displays the properties expected of a transcription factor that is involved in the sustained response of the KAR2 promoter to unfolded proteins in the ER. These experiments show that yeast cells can activate a transcription factor that stimulates expression of a nuclear gene in response to the accumulation of unfolded proteins in another cellular compartment.
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PMID:A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins. 162 22

A family of highly-conserved 70 kDa stress proteins is localized in various intracellular compartments of Saccharomyces cerevisiae. Their gene expression is specifically and/or sometimes cooperatively regulated at the transcriptional level by cis-acting elements found in their respective promoters. Here, we find that depletion of cytosolic Ssa1p induced BiP(Kar2p) in the endoplasmic reticulum at the transcriptional level. By analyzing internal deletion mutants of the KAR2 promoter, we determined that the heat shock element (HSE) is necessary for KAR2 gene induction in response to the depletion of Ssa1p. Furthermore, either the KAR2HSE or SSA1HSE is sufficient for gene activation, as assayed using HSE-CYC1-lacZ fusion reporter plasmids. Finally, temperature-sensitive ssa1 mutants transformed with an HSE-CYC1-lacZ fusion vector exhibited strong induction of beta-galactosidase activity when shifted to a restrictive temperature. These results show that loss of functional Ssa1p from the cytosol up-regulates KAR2 gene expression through an HSE-mediated pathway and also support the idea that SSA1 gene expression is autoregulated.
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PMID:Saccharomyces cerevisiae KAR2 (BiP) gene expression is induced by loss of cytosolic HSP70/Ssa1p through a heat shock element-mediated pathway. 913 28

We screened for genes potentially involved in the secretory and vacuolar pathways a collection of 61 yeast strains, each bearing an essential orphan gene regulated by the tetO7-CYC1 promoter that can be down-regulated by doxycycline. After down-regulating the expression of these genes, we performed systematic Western blot analysis for markers of the secretory and vacuolar pathways that undergo post-translational modifications in their intracellular trafficking. Accumulation of protein precursors, revealed by Western immunoblot analysis, indicates defects in the secretory pathway or in associated biochemical modifications. After screening the whole collection, we identified two genes involved in ER to Golgi trafficking: RER2, a cis-prenyl transferase, and USE1, the function of which was unknown. We demonstrated that repression of USE1 also leads to BiP secretion, and therefore likely affects retrograde, in addition to anterograde, ER to Golgi trafficking. The collection also includes two essential genes involved in intracellular trafficking that were conveniently repressed without resulting growth or trafficking defects.
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PMID:Yeast functional analysis: identification of two essential genes involved in ER to Golgi trafficking. 1291 15