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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 Functional   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
Fis,MazE,MazE-MazF,ppGpp
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MazE-MazF,-](2)


Transcription factor regulation    


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
gaaatttgctCGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911403 [BCE], [GEA], [SM] [1]
  MazE repressor mazEp1 nd -7.0 -36.0 mazE, mazF, mazG
ctacaatgtaGATTGATATATACTGTATCTACATATgatagcggtt
2911363 2911388 [BCE], [GEA], [SM] [1], [2]
  MazE repressor mazEp2 nd -34.0 -50.0 mazE, mazF, mazG
gaaatttgctCGTATCTACAATGTAGATTGATATATACtgtatctaca
2911376 2911403 [BCE], [GEA], [SM] [1]
  MazE repressor mazEp2 nd -20.0 -36.0 mazE, mazF, mazG
ctacaatgtaGATTGATATATACTGTATCTACATATgatagcggtt
2911363 2911388 [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, 2003 Oct

 [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, 2003 Sep 26

 [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, 2001 Mar

 [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, 2002 Jul

 [8] Sat B, Reches M, Engelberg-Kulka H, 2003, The Escherichia coli mazEF suicide module mediates thymineless death., J Bacteriol, 2003 Mar

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

 [10] Zhang J, Zhang Y, Inouye M, 2003, Characterization of the interactions within the mazEF addiction module of Escherichia coli., J Biol Chem, 2003 Aug 22

 [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, 2003 Apr 18

 [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, 2003 Jul 25

 [13] Mittenhuber G, 1999, Occurrence of mazEF-like antitoxin/toxin systems in bacteria., J Mol Microbiol Biotechnol, 1999 Nov

 [14] Santos-Sierra S, Giraldo R, Díaz-Orejas R, 1997, Functional interactions between homologous conditional killer systems of plasmid and chromosomal origin., FEMS Microbiol Lett, 1997 Jul 1

 [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, 1998 Dec 22

 [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-Méndez G, 2003, Distressing bacteria: structure of a prokaryotic detox program., Mol Cell, 2003 Apr

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



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