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MazE DNA-binding transcriptional repressor

Synonyms: MazE
Summary:
MazE is an antitoxin that counteracts the MazF toxin [2, 3]. MazF exhibits ribonuclease activity toward single stranded RNA regions of sequence ACA, and the resulting degradation of cellular mRNA causes global translation inhibition [4]. MazF exhibits RNase activity toward tmRNA, and tmRNA is involved in release of MazF-mediated cell growth inhibition [5].
The mazEF system causes a programmed cell death response to stresses including starvation [3] and antibiotics [6]. The antitoxin, MazE, is subject to degradation by the ClpAP protease complex and exhibits a short (30 minute) half life, whereas the toxin, MazF, is much more stable [3].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MazE     nd nd
Evolutionary Family: MazE
Connectivity class: Local Regulator
Gene name: mazE
  Genome position: 2911091-2911339
  Length: 249 bp / 82 aa
Operon name: relA-mazEFG
TU(s) encoding the TF:
Transcription unit        Promoter
mazEFG
mazEp1
mazEFG
mazEp2
relA-mazEF
relAp1
relA-mazEF
relAp2


Regulon       
Regulated gene(s) mazE, mazF, mazG
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
starvation (3)
defense/survival (2)
other (mechanical, nutritional, oxidative stress) (2)
cell killing (2)
drug resistance/sensitivity (2)
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Regulated operon(s) relA-mazEFG
First gene in the operon(s) mazE, mazE
Simple and complex regulons Fis,MazE,MazE-MazF
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MazE-MazF,-](2)


Transcription factor binding sites (TFBSs) arrangements       

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  MazE repressor mazEp1 nd -21.0 -50.0 mazE, mazF, mazG
aaatttgctcGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911402 [BCE], [GEA], [SM] [1]
  MazE repressor mazEp1 nd -7.0 -36.0 mazE, mazF, mazG
tacaatgtagATTGATATATACTGTATCTACATATgatagcggtt
2911363 2911387 [BCE], [GEA], [SM] [1], [2]
  MazE repressor mazEp2 nd -34.0 -50.0 mazE, mazF, mazG
aaatttgctcGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911402 [BCE], [GEA], [SM] [1]
  MazE repressor mazEp2 nd -20.0 -36.0 mazE, mazF, mazG
tacaatgtagATTGATATATACTGTATCTACATATgatagcggtt
2911363 2911387 [BCE], [GEA], [SM] [1], [2]


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation


Evidence    

 [BCE] Binding of cellular extracts

 [GEA] Gene expression analysis

 [SM] Site mutation



Reference(s)    

 [1] Marianovsky I., Aizenman E., Engelberg-Kulka H., Glaser G., 2001, The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome., J Biol Chem. 276(8):5975-84

 [2] Masuda Y., Miyakawa K., Nishimura Y., Ohtsubo E., 1993, chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R100., J Bacteriol. 175(21):6850-6

 [3] Aizenman E., Engelberg-Kulka H., Glaser G., 1996, An Escherichia coli chromosomal addiction module regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death., Proc Natl Acad Sci U S A. 93(12):6059-63

 [4] Zhang Y., Zhang J., Hoeflich KP., Ikura M., Qing G., Inouye M., 2003, MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli., Mol Cell. 12(4):913-23

 [5] Christensen SK., Pedersen K., Hansen FG., Gerdes K., 2003, Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA., J Mol Biol. 332(4):809-19

 [6] Sat B., Hazan R., Fisher T., Khaner H., Glaser G., Engelberg-Kulka H., 2001, Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality., J Bacteriol. 183(6):2041-5

 [7] Pedersen K., Christensen SK., Gerdes K., 2002, Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins., Mol Microbiol. 45(2):501-10

 [8] Sat B., Reches M., Engelberg-Kulka H., 2003, The Escherichia coli mazEF suicide module mediates thymineless death., J Bacteriol. 185(6):1803-7

 [9] Kamada K., Hanaoka F., Burley SK., 2003, Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition., Mol Cell. 11(4):875-84

 [10] Zhang J., Zhang Y., Inouye M., 2003, Characterization of the interactions within the mazEF addiction module of Escherichia coli., J Biol Chem. 278(34):32300-6

 [11] Lah J., Marianovsky I., Glaser G., Engelberg-Kulka H., Kinne J., Wyns L., Loris R., 2003, Recognition of the intrinsically flexible addiction antidote MazE by a dromedary single domain antibody fragment. Structure, thermodynamics of binding, stability, and influence on interactions with DNA., J Biol Chem. 278(16):14101-11

 [12] Loris R., Marianovsky I., Lah J., Laeremans T., Engelberg-Kulka H., Glaser G., Muyldermans S., Wyns L., 2003, Crystal structure of the intrinsically flexible addiction antidote MazE., J Biol Chem. 278(30):28252-7

 [13] Mittenhuber G., 1999, Occurrence of mazEF-like antitoxin/toxin systems in bacteria., J Mol Microbiol Biotechnol. 1(2):295-302

 [14] Santos-Sierra S., Giraldo R., Diaz-Orejas R., 1997, Functional interactions between homologous conditional killer systems of plasmid and chromosomal origin., FEMS Microbiol Lett. 152(1):51-6

 [15] Engelberg-Kulka H., Reches M., Narasimhan S., Schoulaker-Schwarz R., Klemes Y., Aizenman E., Glaser G., 1998, rexB of bacteriophage lambda is an anti-cell death gene., Proc Natl Acad Sci U S A. 95(26):15481-6

 [16] Metzger S., Dror IB., Aizenman E., Schreiber G., Toone M., Friesen JD., Cashel M., Glaser G., 1988, The nucleotide sequence and characterization of the relA gene of Escherichia coli., J Biol Chem. 263(30):15699-704

 [17] de la Cueva-Mendez G., 2003, Distressing bacteria: structure of a prokaryotic detox program., Mol Cell. 11(4):848-50

 [18] Yamaguchi Y., Park JH., Inouye M., 2011, Toxin-antitoxin systems in bacteria and archaea., Annu Rev Genet. 45:61-79



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