Clp-mediated proteolysis in Gram-positive bacteria is autoregulated by the stability of a repressor

被引:112
作者
Krüger, E
Zühlke, D
Witt, E
Ludwig, H
Hecker, M
机构
[1] Humboldt Univ, Klinikum Charite, Inst Biochem, D-10117 Berlin, Germany
[2] Ernst Moritz Arndt Univ Greifswald, Inst Mikrobiol & Mol Biol, D-17487 Greifswald, Germany
[3] Univ Erlangen Nurnberg, Lehrstuhl Mikrobiol, D-91058 Erlangen, Germany
关键词
Bacillus subtilis; ClpCP protease; heat shock; Hsp; 100; proteolysis;
D O I
10.1093/emboj/20.4.852
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The heat shock proteins ClpC and ClpP are subunits of an ATP-dependent protease of Bacillus subtilis. Under non-stressed conditions, transcription of the clpC and clpP genes is negatively regulated by CtsR, the global repressor of clp gene expression. Here, CtsR was proven to be a specific substrate of the ClpCP protease under stress conditions. Two proteins of former unknown function, McsA and McsB, which are also encoded by the clpC operon, act as modulators of CtsR repression. McsA containing zinc finger motifs stabilizes CtsR under non-stressed conditions. McsB, a putative kinase, can inactivate CtsR by modification to remove the repressor from the DNA and to target CtsR for degradation by the ClpCP protease during stress. Thus, clp gene expression in Gram-positive bacteria is autoregulated by a novel mechanism of controlled proteolysis, a circuit of down-regulation by stabilization and protection of a transcription repressor, and induction by presenting the repressor to the protease, Thereby, the ClpC ATPase, a member of the Hsp100 family, was identified as a positive regulator of the heat shock response.
引用
收藏
页码:852 / 863
页数:12
相关论文
共 63 条
[1]  
BERG JM, 1990, J BIOL CHEM, V265, P6513
[2]  
Bernhardt J, 1999, ELECTROPHORESIS, V20, P2225, DOI 10.1002/(SICI)1522-2683(19990801)20:11<2225::AID-ELPS2225>3.3.CO
[3]  
2-#
[4]   The structures of HsIU and ATP-dependent protease HsIU-HsIV [J].
Bochtler, M ;
Hartmann, C ;
Song, HK ;
Bourenkov, GP ;
Bartunik, HD ;
Huber, R .
NATURE, 2000, 403 (6771) :800-805
[5]   CONSTRUCTION AND CHARACTERIZATION OF NEW CLONING VEHICLES .2. MULTIPURPOSE CLONING SYSTEM [J].
BOLIVAR, F ;
RODRIGUEZ, RL ;
GREENE, PJ ;
BETLACH, MC ;
HEYNEKER, HL ;
BOYER, HW ;
CROSA, JH ;
FALKOW, S .
GENE, 1977, 2 (02) :95-113
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]  
BUKAU B, 2000, GUIDEBOOK MOL CHAPER, P525
[8]   The ubiquitin-proteasome pathway: on protein death and cell life [J].
Ciechanover, A .
EMBO JOURNAL, 1998, 17 (24) :7151-7160
[9]   ClpE, a novel type of HSP100 ATPase, is part of the CtsR heat shock regulon of Bacillus subtilis [J].
Derré, I ;
Rapoport, G ;
Devine, K ;
Rose, M ;
Msadek, T .
MOLECULAR MICROBIOLOGY, 1999, 32 (03) :581-593
[10]   The CtsR regulator of stress response is active as a dimer and specifically degraded in vivo at 37°C [J].
Derré, I ;
Rapoport, G ;
Msadek, T .
MOLECULAR MICROBIOLOGY, 2000, 38 (02) :335-347