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)

It has been shown previously that growth and endoplasmic reticulum (ER) translocation defects occur in response to depletion of the 54-kDa subunit of signal recognition particle (SRP54) in Saccharomyces cerevisiae (Hann, B. B., and Walter, P. (1991) Cell 67, 131-144). We report here that cells depleted of SRP54p undergo a general stress response, the onset of which is observed almost two-cell doublings after SRP54 protein levels fall below the limits of detection. The stress response to SRP54p depletion occurs in two distinct phases, unlike the response to other stressors such as heat shock. In the initial phase, the cytoplasmic Hsp70 levels are drastically increased coincident with an abrupt slowing of growth and accumulation of untranslocated species of the ER-resident chaperone BiP. During this first response, levels of the yeast DnaJ homolog Ydj1p are also increased. In the second phase, which is detected 5 h later, levels of the cytoplasmic heat shock proteins Hsp82 and Hsp104 are increased. BiP is also induced during this second phase, while the ER levels of the resident foldase protein disulfide isomerase are significantly reduced. Since only those cytoplasmic stress proteins which have been shown to participate in membrane translocation are induced in the first phase, these findings indicate the presence of a stress response specific to accumulation of secretory protein precursors in the cytoplasm.
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PMID:The stress response to loss of signal recognition particle function in Saccharomyces cerevisiae. 798 55

In Saccharomyces cerevisiae Ydj1p, a DnaJ homolog, is localized to the cytosol with the Ssa and Ssb Hsp70 proteins. Ydj1p helps facilitate polypeptide translocation across mitochondrial and endoplasmic reticulum membranes (Caplan, A. J., Cyr, D. M., and Douglas, M. G. (1992) Cell 71, 1143-1155) and can directly interact with Ssa1p to regulate chaperone activity (Cyr, D. M., Lu, X., and Douglas, M. G. (1992) J. Biol. Chem. 267, 20927-20931). In this study, the role of Ydj1p in modulating ATP-dependent reactions catalyzed by Ssa and Ssb Hsp70 proteins has been examined using purified components and compared with that of other Hsp70 homologs BiP and DnaK. Ssa1p, Ssa2p, and Ssb1/2p all formed stable complexes with the mitochondrial presequence peptide, F1 beta(1-51). ATP alone had only modest effects on polypeptide complex formation with Ssa1p and Ssa2p, but prevented the majority of polypeptide binding to BiP and DnaK. ATP by itself also reduced polypeptide binding to Ssb1/2p to a level that was intermediate between that observed for the Ssa Hsp70 proteins tested and BiP and DnaK. ATP hydrolysis by Ssa1p, Ssa2p, and Ssb1/2p occurred at similar rates. Ydj1p was a potent modulator of the both the ATPase and polypeptide binding activities of Ssa1p and Ssa2p. In contrast, Ydj1p had little effect on the ATPase and polypeptide binding activity of Ssb1/2p. Therefore the chaperone-related activities of Ssa and Ssb Hsp70 proteins exhibit significant differences in sensitivity to ATP and YDJ1p. These data indicate that regulation of Hsp70 activity by DnaJ homologs can be specific. The specificity of interactions between Ydj1p and the Ssa and Ssb Hsp70 proteins observed could contribute in determining the functional specificity of these chaperones in the cytosol. In related experiments, F1 beta(1-51) was found to reduce the extent to which Ydj1p stimulated Ssa1p ATPase activity. This effect correlated with the formation of F1 beta(1-51).Ssa1p complexes. We propose that intramolecular communication between the polypeptide binding, ATPase and DnaJ regulatory domains on Ssa1p plays a role in the regulation of chaperone activity.
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PMID:Differential regulation of Hsp70 subfamilies by the eukaryotic DnaJ homologue YDJ1. 814 72

The translocation of a secretory precursor protein across the ER membrane comprises three phases: docking of the precursor at the membrane, insertion into the translocation pore, and exit from the pore into the ER lumen. We demonstrate that Sec62p, Sec71p and Sec72p form a translocon subcomplex that engages secretory precursors at the membrane site of the ER translocation machinery. Binding of a precursor to the subcomplex depends on the presence of an intact signal sequence and occurs only in the absence of ATP. In the presence of ATP, the precursor is released from the subcomplex in a reaction mediated by the lumenal hsp70, BiP. This release reaction, which is specific to BiP and requires interaction between BiP and the DnaJ homolog Sec63p, defines a role for BiP and Sec63p early in the ER translocation process.
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PMID:Binding of secretory precursor polypeptides to a translocon subcomplex is regulated by BiP. 901 9