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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The heat shock response of Escherichia coli is regulated by the cellular level and the activity of sigma32, an alternative sigma factor for heat shock promoters. FtsH, a membrane-bound AAA-type metalloprotease, degrades sigma32 and has a central role in the control of the sigma32 level. The ftsH null mutant was isolated, and establishment of the DeltaftsH mutant allowed us to investigate control mechanisms of the stability and the activity of sigma32 separately in vivo. Loss of the FtsH function caused marked stabilization and consequent accumulation of sigma32 ( approximately 20-fold of the wild type), leading to the impaired downregulation of the level of sigma32. Surprisingly, however, DeltaftsH cells express heat shock proteins only two- to threefold higher than wild-type cells, and they also show almost normal heat shock response upon temperature upshift. These results indicate the presence of a control mechanism that downregulates the activity of sigma32 when it is accumulated. Overproduction of DnaK/J reduces the activity of sigma32 in DeltaftsH cells without any detectable changes in the level of sigma32, indicating that the DnaK chaperone system is responsible for the activity control of sigma32 in vivo. In addition, CbpA, an analogue of DnaJ, was demonstrated to have overlapping functions with DnaJ in both the activity and the stability control of sigma32.
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PMID:Heat shock regulation in the ftsH null mutant of Escherichia coli: dissection of stability and activity control mechanisms of sigma32 in vivo. 982 23

The Escherichia coli sigma 32 transcriptional regulator has been shown to be degraded both in vivo and in vitro by the FtsH (HflB) protease, a member of the AAA protein family. In our attempts to study this process in detail, we found that two sigma 32 mutants lacking 15-20 C-terminal amino acids had substantially increased half-lives in vivo or in vitro, compared with wild-type sigma 32. A truncated version of sigma 32, sigma 32 C delta, was purified to homogeneity and shown to be resistant to FtsH-dependent degradation in vitro, suggesting that FtsH initiates sigma 32 degradation from its extreme C-terminal region. Purified sigma 32 C delta interacted with the DnaK and DnaJ chaperone proteins in a fashion similar to that of wild-type sigma 32. However, in contrast to wild-type sigma 32, sigma 32 C delta was largely deficient in its in vivo and in vitro interaction with core RNA polymerase. As a consequence, the truncated sigma 32 protein was completely non-functional in vivo, even when overproduced. Furthermore, it is shown that wild-type sigma 32 is protected from degradation by FtsH when complexed to the RNA polymerase core, but sensitive to proteolysis when in complex with the DnaK chaperone machine. Our results are in agreement with the proposal that the capacity of the DnaK chaperone machine to autoregulate its own synthesis negatively is simply the result of its ability to sequester sigma 32 from RNA polymerase, thus making it accessible to degradation by the FtsH protease.
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PMID:On the mechanism of FtsH-dependent degradation of the sigma 32 transcriptional regulator of Escherichia coli and the role of the Dnak chaperone machine. 998 18

Under non-stressed conditions in Escherichia coli, the heat shock transcription factor sigma(32) is rapidly degraded by the AAA protease FtsH. The DnaK chaperone system is also required for the rapid turnover of sigma(32) in the cell. It has been hypothesized that the DnaK chaperone system facilitates the degradation of sigma(32) by sequestering it from RNA polymerase core. This hypothesis predicts that mutant sigma(32) proteins, which are deficient in binding to RNA polymerase core, will be degraded independently of the DnaK chaperone system. We examined the in vivo stability of such mutant sigma(32) proteins. Results indicated that the mutant sigma(32) proteins as similar as authentic sigma(32) were stabilized in DeltadnaK and DeltadnaJ/DeltacbpA cells. The interaction between sigma(32) and DnaK/DnaJ/GrpE was not affected by these mutations. These results strongly suggest that the degradation of sigma(32) requires an unidentified active role of the DnaK chaperone system.
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PMID:Evidence for an active role of the DnaK chaperone system in the degradation of sigma(32). 1093 May 81

A key step in the regulation of heat shock genes in Escherichia coli is the stress-dependent degradation of the heat shock promoter-specific sigma(32) subunit of RNA polymerase by the AAA protease, FtsH. Previous studies implicated the C termini of protein substrates, including sigma(32), as degradation signals for AAA proteases. We investigated the role of the C terminus of sigma(32) in FtsH-dependent degradation by analysis of C-terminally truncated sigma(32) mutant proteins. Deletion of the 5, 11, 15, and 21 C-terminal residues of sigma(32) did not affect degradation in vivo or in vitro. Furthermore, a peptide comprising the C-terminal 21 residues of sigma(32) was not degraded by FtsH in vitro and thus did not serve as a recognition sequence for the protease, while an unrelated peptide of similar length was efficiently degraded. The truncated sigma(32) mutant proteins remained capable of associating with DnaK and DnaJ in vitro but showed intermediate (5-amino-acid deletion) and strong (11-, 15-, and 21-amino-acid deletions) defects in association with RNA polymerase in vitro and biological activity in vivo. These results indicate an important role for the C terminus of sigma(32) in RNA polymerase binding but no essential role for FtsH-dependent degradation and association of chaperones.
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PMID:The C terminus of sigma(32) is not essential for degradation by FtsH. 1156 90

All living organisms respond to environmental stresses, such as heat or ethanol by increasing the synthesis of a specific group of proteins termed heat shock proteins (Hsps) or stress proteins. Major Hsps are molecular chaperones and proteases. Molecular chaperones facilitate the proper folding of polypeptides, protect other proteins from inactivation, and reactivate aggregated proteins. Heat shock proteases eliminate proteins irreversibly damaged by stress. This review describes the role of heat shock proteins of the model bacterial cell, E. coli in the protection of other proteins against aggregation and in the mechanism of removal of protein aggregates from the cell. This mechanism remains unclear and it is believed to involve substrate renaturation and proteolysis by molecular chaperones and heat shock proteases. Recently, many studies have been focused on the disaggregation and reactivation of proteins by a bi-chaperone system consisting of DnaK/DnaJ/GrpE and ClpB, an ATPase from the AAA superfamily of proteins.
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PMID:[Role of Escherichia coli molecular chaperones in the protection of bacterial cells against irreversible aggregation induced by heat shock]. 1620 52