Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of Bacillus subtilis aprE, encoding an extracellular alkaline protease, is positively regulated by phosphorylated DegU, the regulator of a two-component regulatory system, DegS-DegU. We found that the expression of an aprE'-'lacZ fusion was greatly reduced in a disruption mutant with a mutation of relA, which encodes the stringent factor RelA. The level of DegU in the relA mutant was similar to that in the wild-type cell. A relA degU double mutation did not result in a further decrease of the aprE'-'lacZ level found in a degU single mutant. The expression of the aprE'-'lacZ fusion in the relA mutant was stimulated by multicopy degR or the degU32(Hy) and degS200(Hy) mutations that cause the stabilization of phosphorylated DegU. Furthermore, the expression of sacB'-'lacZ, which is also dependent on phosphorylated DegU, was stimulated by the relA mutation, and this stimulation was not seen in the relA degU double mutant. These results show that RelA (or its product guanosine-3',5'-bisdiphosphate [pp Gpp]) does not affect the phosphorylation of DegU and suggest that it participates in the expression of aprE and sacB through the regulation of DegU-dependent transcription.
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PMID:Involvement of stringent factor RelA in expression of the alkaline protease gene aprE in Bacillus subtilis. 1144 1

Expression of the Bacillus subtilis alkaline protease gene aprE is controlled by many positive and negative regulators at the transcriptional level. During the course of screening for organic compounds that affect the expression of a translational aprE'-'lacZ fusion, we found that lincomycin (Lm), erythromycin and chloramphenicol exhibited an inhibitory effect in concentrations that hardly affected cell growth. The antibiotics are known to inhibit protein synthesis by binding to ribosomes. We chose one of them, Lm, for further study. We have previously shown that aprE expression requires guanosine 3',5'-bisdiphosphate (ppGpp) synthesized on the ribosome by the stringent factor RelA. An examination of Lm-treated cells showed that the levels of ppGpp were greatly reduced in these cells, and the inhibitory effect of the antibiotic was not seen in relA-disruption mutants. Transcriptional levels of aprE, however, were not influenced by Lm treatment as shown by using a transcriptional aprE-lacZ fusion as well as quantitative RT-PCR. Furthermore, disruption of relA did not affect the expression of transcriptional aprE-lacZ. From these results, we conclude that aprE expression is controlled by the stringent control at the posttranscriptional level, and that Lm inhibits this process by inhibiting ppGpp synthesis on the ribosome.
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PMID:Inhibition of Bacillus subtilis aprE expression by lincomycin at the posttranscriptional level through inhibition of ppGpp synthesis. 1468 35