Regulated Proteolysis: Control of the Escherichia coli σE-Dependent Cell Envelope Stress Response

  • Sarah E. Barchinger
  • Sarah E. Ades
Part of the Subcellular Biochemistry book series (SCBI, volume 66)


Over the past decade, regulatory proteolysis has emerged as a paradigm for transmembrane signal transduction in all organisms, from bacteria to humans. These conserved proteolytic pathways share a common design that involves the sequential proteolysis of a membrane-bound regulatory protein by two proteases. Proteolysis releases the regulator, which is inactive in its membrane-bound form, into the cytoplasm where it performs its cellular function. One of the best-characterized examples of signal transduction via regulatory proteolysis is the pathway governing the σE-dependent cell envelope stress response in Escherichia coli. In unstressed cells, σE is sequestered at the membrane by the transmembrane anti-sigma factor, RseA. Stresses that compromise the cell envelope and interfere with the proper folding of outer membrane proteins (OMPs) activate the proteolytic pathway. The C-terminal residues of unfolded OMPs bind to the inner membrane protease, DegS, to initiate the proteolytic cascade. DegS removes the periplasmic domain of RseA creating a substrate for the next protease in the pathway, RseP. RseP cleaves RseA in the periplasmic region in a process called regulated intramembrane proteolysis (RIP). The remaining fragment of RseA is released into the cytoplasm and fully degraded by the ATP-dependent protease, ClpXP, with the assistance of the adaptor protein, SspB, thereby freeing σE to reprogram gene expression. A growing body of evidence indicates that the overall proteolytic framework that governs the σE response is used to regulate similar anti-sigma factor/sigma factor pairs throughout the bacterial world and has been adapted to recognize a wide variety of signals and control systems as diverse as envelope stress responses, sporulation, virulence, and iron-siderophore uptake. In this chapter, we review the extensive physiological, biochemical, and structural studies on the σE system that provide remarkable insights into the mechanistic underpinnings of this regulated proteolytic signal transduction pathway. These studies reveal design principles that are applicable to related proteases and regulatory proteolytic pathways in all domains of life.


Protease Domain Proteolytic Pathway Oxyanion Hole Proteolytic Cascade Envelope Stress 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Literature Cited

  1. 1.
    Brown MS, Ye J, Rawson RB, Goldstein JL (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100(4):391–398PubMedGoogle Scholar
  2. 2.
    Chen G, Zhang X (2010) New insights into S2P signaling cascades: regulation, variation, and conservation. Protein Sci 19(11):2015–2030PubMedGoogle Scholar
  3. 3.
    Ehrmann M, Clausen T (2004) Proteolysis as a regulatory mechanism. Annu Rev Genet 38:709–724PubMedGoogle Scholar
  4. 4.
    Brown MS, Goldstein JL (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89(3):331–340PubMedGoogle Scholar
  5. 5.
    Brown MS, Goldstein JL (1999) A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci U S A 96(20):11041–11048PubMedGoogle Scholar
  6. 6.
    Rudner DZ, Fawcett P, Losick R (1999) A family of membrane-embedded metalloproteases involved in regulated proteolysis of membrane-associated transcription factors. Proc Natl Acad Sci U S A 96(26):14765–14770PubMedGoogle Scholar
  7. 7.
    Cutting S, Roels S, Losick R (1991) Sporulation operon spoIVF and the characterization of mutations that uncouple mother-cell from forespore gene expression in Bacillus subtilis. J Mol Biol 221(4):1237–1256PubMedGoogle Scholar
  8. 8.
    Ricca E, Cutting S, Losick R (1992) Characterization of bofA, a gene involved in intercompartmental regulation of pro-sigma K processing during sporulation in Bacillus subtilis. J Bacteriol 174(10):3177–3184PubMedGoogle Scholar
  9. 9.
    Campo N, Rudner DZ (2007) SpoIVB and CtpB are both forespore signals in the activation of the sporulation transcription factor sigmaK in Bacillus subtilis. J Bacteriol 189(16):6021–6027PubMedGoogle Scholar
  10. 10.
    Zhou R, Kroos L (2005) Serine proteases from two cell types target different components of a complex that governs regulated intramembrane proteolysis of pro-sigmaK during Bacillus subtilis development. Mol Microbiol 58(3):835–846PubMedGoogle Scholar
  11. 11.
    Molière N, Turgay K (2013) General and regulatory proteolysis in Bacillus subtilis. In: Dougan DA (ed) Regulated proteolysis: from bacteria to yeast. Springer, Subcell Biochem 66:73–103Google Scholar
  12. 12.
    Ades SE (2006) AAA+  molecular machines: firing on all cylinders. Curr Biol 16(2):R46–R48PubMedGoogle Scholar
  13. 13.
    Alba BM, Gross CA (2004) Regulation of the Escherichia coli sigma-dependent envelope stress response. Mol Microbiol 52(3):613–619PubMedGoogle Scholar
  14. 14.
    Alba B, Leeds J, Onufryk C, Lu C et al (2002) DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma’E-dependent extracytoplasmic stress response. Genes Dev 16:2156–2168PubMedGoogle Scholar
  15. 15.
    Kanehara K, Ito K, Akiyama Y (2002) YaeL (EcfE) activates the sigmaE pathway of stress response through a site-2 cleavage of anti-sigma’E, RseA. Genes Dev 16:2147–2155PubMedGoogle Scholar
  16. 16.
    Ades SE (2004) Control of the alternative sigma factor sigmaE in Escherichia coli. Curr Opin Microbiol 7(2):157–162PubMedGoogle Scholar
  17. 17.
    Flynn JM, Levchenko I, Sauer RT, Baker TA (2004) Modulating substrate choice: the SspB adaptor delivers a regulator of the extracytoplasmic-stress response to the AAA+  protease ClpXP for degradation. Genes Dev 18(18):2292–2301PubMedGoogle Scholar
  18. 18.
    Silhavy TJ, Kahne D, Walker S (2010) The bacterial cell envelope. Cold Spring Harb Perspect Biol 2(5):a000414PubMedGoogle Scholar
  19. 19.
    MacRitchie DM, Buelow DR, Price NL, Raivio TL (2008) Two-component signaling and gram negative envelope stress response systems. Adv Exp Med Biol 631:80–110PubMedGoogle Scholar
  20. 20.
    Rowley G, Spector M, Kormanec J, Roberts M (2006) Pushing the envelope: extracytoplasmic stress responses in bacterial pathogens. Nat Rev Microbiol 4(5):383–394PubMedGoogle Scholar
  21. 21.
    De Las Penas A, Connolly L, Gross CA (1997) SigmaE is an essential sigma factor in Escherichia coli. J Bacteriol 179(21):6862–6864Google Scholar
  22. 22.
    Hayden JD, Ades SE (2008) The extracytoplasmic stress factor, sigma, is required to maintain cell envelope integrity in Escherichia coli. PLoS One 3(2):e1573PubMedGoogle Scholar
  23. 23.
    Gruber TM, Gross CA (2003) Multiple sigma subunits and the partitioning of bacterial transcription space. Annu Rev Microbiol 57:441–466PubMedGoogle Scholar
  24. 24.
    Helmann JD (2002) The extracytoplasmic function (ECF) sigma factors. Adv Microb Physiol 46:47–110PubMedGoogle Scholar
  25. 25.
    Erickson JW, Gross CA (1989) Identification of the sigma E subunit of Escherichia coli RNA polymerase: a second alternate sigma factor involved in high-temperature gene expression. Genes Dev 3(9):1462–1471PubMedGoogle Scholar
  26. 26.
    Micevski D, Dougan DA (2013) Proteolytic regulation of stress response pathways in Escherichia coli. In: Dougan DA (ed) Regulated proteolysis: from bacteria to yeast. Springer, Subcell Biochem 66:105–128Google Scholar
  27. 27.
    Mecsas J, Rouviere PE, Erickson JW, Donohue TJ et al (1993) The activity of sigma E, an Escherichia coli heat-inducible sigma-factor, is modulated by expression of outer membrane proteins. Genes Dev 7(12B):2618–2628PubMedGoogle Scholar
  28. 28.
    Missiakas D, Betton JM, Raina S (1996) New components of protein folding in extracytoplasmic compartments of Escherichia coli SurA, FkpA and Skp/OmpH. Mol Microbiol 21(4):871–884PubMedGoogle Scholar
  29. 29.
    Raina S, Missiakas D, Georgopoulos C (1995) The rpoE gene encoding the sigma E (sigma 24) heat shock sigma factor of Escherichia coli. EMBO J 14(5):1043–1055PubMedGoogle Scholar
  30. 30.
    Rouviere PE, Gross CA (1996) SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins. Genes Dev 10(24):3170–3182PubMedGoogle Scholar
  31. 31.
    Connolly L, De Las PA, Alba BM, Gross CA (1997) The response to extracytoplasmic stress in Escherichia coli is controlled by partially overlapping pathways. Genes Dev 11(15):2012–2021PubMedGoogle Scholar
  32. 32.
    Raivio TL, Silhavy TJ (1999) The sigmaE and Cpx regulatory pathways: overlapping but distinct envelope stress responses. Curr Opin Microbiol 2(2):159–165PubMedGoogle Scholar
  33. 33.
    Ruiz N, Silhavy TJ (2005) Sensing external stress: watchdogs of the Escherichia coli cell envelope. Curr Opin Microbiol 8(2):122–126PubMedGoogle Scholar
  34. 34.
    Mecsas J, Welch R, Erickson JW, Gross CA (1995) Identification and characterization of an outer membrane protein, OmpX, in Escherichia coli that is homologous to a family of outer membrane proteins including Ail of Yersinia enterocolitica. J Bacteriol 177(3):799–804PubMedGoogle Scholar
  35. 35.
    Staron A, Sofia HJ, Dietrich S, Ulrich LE et al (2009) The third pillar of bacterial signal transduction: classification of the extracytoplasmic function (ECF) sigma factor protein family. Mol Microbiol 74(3):557–581PubMedGoogle Scholar
  36. 36.
    Davis BM, Waldor MK (2009) High-throughput sequencing reveals suppressors of Vibrio cholerae rpoE mutations: one fewer porin is enough. Nucleic Acids Res 37(17):5757–5767PubMedGoogle Scholar
  37. 37.
    Heusipp G, Schmidt MA, Miller VL (2003) Identification of rpoE and nadB as host responsive elements of Yersinia enterocolitica. FEMS Microbiol Lett 226(2):291–298PubMedGoogle Scholar
  38. 38.
    Humphreys S, Stevenson A, Bacon A, Weinhardt AB et al (1999) The alternative sigma factor, sigmaE, is critically important for the virulence of Salmonella typhimurium. Infect Immun 67(4):1560–1568PubMedGoogle Scholar
  39. 39.
    Testerman TL, Vazquez-Torres A, Xu Y, Jones-Carson J et al (2002) The alternative sigma factor sigmaE controls antioxidant defences required for Salmonella virulence and stationary-phase survival. Mol Microbiol 43(3):771–782PubMedGoogle Scholar
  40. 40.
    Barchinger SE, Zhang X, Hester SE, Rodriguez ME, Harvill ET, Ades SE (2012) sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice. BMC Microbiol 12:179Google Scholar
  41. 41.
    Raivio TL (2005) Envelope stress responses and Gram-negative bacterial pathogenesis. Mol Microbiol 56(5):1119–1128PubMedGoogle Scholar
  42. 42.
    Rhodius VA, Suh WC, Nonaka G, West J et al (2006) Conserved and variable functions of the sigmaE stress response in related genomes. PLoS Biol 4(1):e2PubMedGoogle Scholar
  43. 43.
    Johansen J, Rasmussen AA, Overgaard M, Valentin-Hansen P (2006) Conserved small non-coding RNAs that belong to the sigmaE regulon: role in down-regulation of outer membrane proteins. J Mol Biol 364(1):1–8PubMedGoogle Scholar
  44. 44.
    Thompson KM, Rhodius VA, Gottesman S (2007) SigmaE regulates and is regulated by a small RNA in Escherichia coli. J Bacteriol 189(11):4243–4256PubMedGoogle Scholar
  45. 45.
    Vogel J, Papenfort K (2006) Small non-coding RNAs and the bacterial outer membrane. Curr Opin Microbiol 9(6):605–611PubMedGoogle Scholar
  46. 46.
    Rigel NW, Silhavy TJ (2012) Making a beta-barrel: assembly of outer membrane proteins in Gram-negative bacteria. Curr Opin Microbiol 15(2):189–193PubMedGoogle Scholar
  47. 47.
    Ruiz N, Kahne D, Silhavy TJ (2006) Advances in understanding bacterial outer-membrane biogenesis. Nat Rev Microbiol 4(1):57–66PubMedGoogle Scholar
  48. 48.
    Kovacikova G, Skorupski K (2002) The alternative sigma factor sigma(E) plays an important role in intestinal survival and virulence in Vibrio cholerae. Infect Immun 70(10):5355–5362PubMedGoogle Scholar
  49. 49.
    Miticka H, Rowley G, Rezuchova B, Homerova D et al (2003) Transcriptional analysis of the rpoE gene encoding extracytoplasmic stress response sigma factor sigmaE in Salmonella enterica serovar Typhimurium. FEMS Microbiol Lett 226(2):307–314PubMedGoogle Scholar
  50. 50.
    Rouviere PE, De Las Penas A, Mecsas J, Lu CZ et al (1995) rpoE, the gene encoding the second heat-shock sigma factor, sigma E, in Escherichia coli. EMBO J 14(5):1032–1042PubMedGoogle Scholar
  51. 51.
    Schurr MJ, Yu H, Boucher JC, Hibler NS et al (1995) Multiple promoters and induction by heat shock of the gene encoding the alternative sigma factor AlgU (sigma E) which controls mucoidy in cystic fibrosis isolates of Pseudomonas aeruginosa. J Bacteriol 177(19):5670–5679PubMedGoogle Scholar
  52. 52.
    De Las PA, Connolly L, Gross CA (1997) The sigmaE-mediated response to extracytoplasmic stress in Escherichia coli is transduced by RseA and RseB, two negative regulators of sigmaE. Mol Microbiol 24(2):373–385Google Scholar
  53. 53.
    Missiakas D, Mayer MP, Lemaire M, Georgopoulos C et al (1997) Modulation of the Escherichia coli sigmaE (RpoE) heat-shock transcription-factor activity by the RseA, RseB and RseC proteins. Mol Microbiol 24(2):355–371PubMedGoogle Scholar
  54. 54.
    Campbell EA, Tupy JL, Gruber TM, Wang S et al (2003) Crystal structure of Escherichia coli sigmaE with the cytoplasmic domain of its anti-sigma RseA. Mol Cell 11(4):1067–1078PubMedGoogle Scholar
  55. 55.
    Schrodinger LLC (2010) The PyMOL molecular graphics system, Version 1.3r1Google Scholar
  56. 56.
    Paget MS, Helmann JD (2003) The sigma70 family of sigma factors. Genome Biol 4(1):203PubMedGoogle Scholar
  57. 57.
    Chaba R, Grigorova IL, Flynn JM, Baker TA et al (2007) Design principles of the proteolytic cascade governing the sigmaE-mediated envelope stress response in Escherichia coli: keys to graded, buffered, and rapid signal transduction. Genes Dev 21(1):124–136PubMedGoogle Scholar
  58. 58.
    Maeda H, Fujita N, Ishihama A (2000) Competition among seven Escherichia coli sigma subunits: relative binding affinities to the core RNA polymerase. Nucleic Acids Res 28(18):3497–3503PubMedGoogle Scholar
  59. 59.
    Grigorova IL, Chaba R, Zhong HJ, Alba BM et al (2004) Fine-tuning of the Escherichia coli sigmaE envelope stress response relies on multiple mechanisms to inhibit signal-independent proteolysis of the transmembrane anti-sigma factor, RseA. Genes Dev 18(21):2686–2697PubMedGoogle Scholar
  60. 60.
    Cezairliyan BO, Sauer RT (2007) Inhibition of regulated proteolysis by RseB. Proc Natl Acad Sci U S A 104(10):3771–3776PubMedGoogle Scholar
  61. 61.
    Chaba R, Alba BM, Guo MS, Sohn J et al (2011) Signal integration by DegS and RseB governs the σ E-mediated envelope stress response in Escherichia coli. Proc Natl Acad Sci U S A 108(5):2106–2111PubMedGoogle Scholar
  62. 62.
    Ades SE, Connolly LE, Alba BM, Gross CA (1999) The Escherichia coli sigma(E)-dependent extracytoplasmic stress response is controlled by the regulated proteolysis of an anti-sigma factor. Genes Dev 13(18):2449–2461PubMedGoogle Scholar
  63. 63.
    Ades SE, Grigorova IL, Gross CA (2003) Regulation of the alternative sigma factor sigma(E) during initiation, adaptation, and shutoff of the extracytoplasmic heat shock response in Escherichia coli. J Bacteriol 185(8):2512–2519PubMedGoogle Scholar
  64. 64.
    Alba BM, Zhong HJ, Pelayo JC, Gross CA (2001) degS (hhoB) is an essential Escherichia coli gene whose indispensable function is to provide sigma (E) activity. Mol Microbiol 40(6):1323–1333PubMedGoogle Scholar
  65. 65.
    Kanehara K, Akiyama Y, Ito K (2001) Characterization of the yaeL gene product and its S2P-protease motifs in Escherichia coli. Gene 281(1–2):71–79PubMedGoogle Scholar
  66. 66.
    Flynn JM, Neher SB, Kim YI, Sauer RT et al (2003) Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals. Mol Cell 11(3):671–683PubMedGoogle Scholar
  67. 67.
    Levchenko I, Grant RA, Flynn JM, Sauer RT et al (2005) Versatile modes of peptide recognition by the AAA+  adaptor protein SspB. Nat Struct Mol Biol 12(6):520–525PubMedGoogle Scholar
  68. 68.
    Bohn C, Collier J, Bouloc P (2004) Dispensable PDZ domain of Escherichia coli YaeL essential protease. Mol Microbiol 52(2):427–435PubMedGoogle Scholar
  69. 69.
    Kanehara K, Ito K, Akiyama Y (2003) YaeL proteolysis of RseA is controlled by the PDZ domain of YaeL and a Gln-rich region of RseA. EMBO J 22(23):6389–6398PubMedGoogle Scholar
  70. 70.
    Walsh N, Alba B, Bose B, Gross C et al (2003) OMP peptide signals initiate the envelope-stress response by activating DegS protease via relief of inhibition mediated by its PDZ domain. Cell 113:61–71PubMedGoogle Scholar
  71. 71.
    Clausen T, Kaiser M, Huber R, Ehrmann M (2011) HTRA proteases: regulated proteolysis in protein quality control. Nat Rev Mol Cell Biol 12(3):152–162PubMedGoogle Scholar
  72. 72.
    Wilken C, Kitzing K, Kurzbauer R, Ehrmann M et al (2004) Crystal structure of the DegS stress sensor: how a PDZ domain recognizes misfolded protein and activates a protease. Cell 117(4):483–494PubMedGoogle Scholar
  73. 73.
    Zeth K (2004) Structural analysis of DegS, a stress sensor of the bacterial periplasm. FEBS Lett 569(1–3):351–358PubMedGoogle Scholar
  74. 74.
    Cowan SW, Garavito RM, Jansonius JN, Jenkins JA et al (1995) The structure of OmpF porin in a tetragonal crystal form. Structure 3(10):1041–1050PubMedGoogle Scholar
  75. 75.
    Hagan CL, Silhavy TJ, Kahne D (2011) beta-Barrel membrane protein assembly by the Bam complex. Annu Rev Biochem 80:189–210PubMedGoogle Scholar
  76. 76.
    Rezuchova B, Miticka H, Homerova D, Roberts M et al (2003) New members of the Escherichia coli sigmaE regulon identified by a two-plasmid system. FEMS Microbiol Lett 225(1):1–7PubMedGoogle Scholar
  77. 77.
    Collinet B, Yuzawa H, Chen T, Herrera C et al (2000) RseB binding to the periplasmic domain of RseA modulates the RseA:sigmaE interaction in the cytoplasm and the availability of sigmaE.RNA polymerase. J Biol Chem 275(43):33898–33904PubMedGoogle Scholar
  78. 78.
    Wollmann P, Zeth K (2007) The structure of RseB: a sensor in periplasmic stress response of E. coli. J Mol Biol 372(4):927–941PubMedGoogle Scholar
  79. 79.
    Kim DY, Kwon E, Choi J, Hwang H-Y et al (2010) Structural basis for the negative regulation of bacterial stress response by RseB. Protein Sci 19(6):1258–1263PubMedGoogle Scholar
  80. 80.
    Kim DY, Jin KS, Kwon E, Ree M et al (2007) Crystal structure of RseB and a model of its binding mode to RseA. Proc Natl Acad Sci U S A 104(21):8779–8784PubMedGoogle Scholar
  81. 81.
    Sohn J, Grant RA, Sauer RT (2007) Allosteric activation of DegS, a stress sensor PDZ protease. Cell 131(3):572–583PubMedGoogle Scholar
  82. 82.
    Sohn J, Sauer RT (2009) OMP peptides modulate the activity of DegS protease by differential binding to active and inactive conformations. Mol Cell 33(1):64–74PubMedGoogle Scholar
  83. 83.
    Sohn J, Grant RA, Sauer RT (2009) OMP peptides activate the DegS stress-sensor protease by a relief of inhibition mechanism. Structure 17(10):1411–1421PubMedGoogle Scholar
  84. 84.
    Sohn J, Grant RA, Sauer RT (2010) Allostery is an intrinsic property of the protease domain of DegS: implications for enzyme function and evolution. J Biol Chem 285(44):34039–34047PubMedGoogle Scholar
  85. 85.
    Hasselblatt H, Kurzbauer R, Wilken C, Krojer T et al (2007) Regulation of the E stress response by DegS: how the PDZ domain keeps the protease inactive in the resting state and allows integration of different OMP-derived stress signals upon folding stress. Genes Dev 21(20):2659–2670PubMedGoogle Scholar
  86. 86.
    Monod J, Wyman J, Changeux JP (1965) On the nature of allosteric transitions: a plausible model. J Mol Biol 12:88–118PubMedGoogle Scholar
  87. 87.
    Cui Q, Karplus M (2008) Allostery and cooperativity revisited. Protein Sci 17(8):1295–1307PubMedGoogle Scholar
  88. 88.
    Kinch LN, Ginalski K, Grishin NV (2006) Site-2 protease regulated intramembrane proteolysis: sequence homologs suggest an ancient signaling cascade. Protein Sci 15(1):84–93PubMedGoogle Scholar
  89. 89.
    Koide K, Ito K, Akiyama Y (2008) Substrate recognition and binding by RseP, an Escherichia coli intramembrane protease. J Biol Chem 283(15):9562–9570PubMedGoogle Scholar
  90. 90.
    Inaba K, Suzuki M, Maegawa K, Akiyama S et al (2008) A pair of circularly permutated PDZ domains control RseP, the S2P family intramembrane protease of Escherichia coli. J Biol Chem 283(50):35042–35052PubMedGoogle Scholar
  91. 91.
    Li X, Wang B, Feng L, Kang H et al (2009) Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage. Proc Natl Acad Sci U S A 106(35):14837–14842PubMedGoogle Scholar
  92. 92.
    Feng L, Yan H, Wu Z, Yan N et al (2007) Structure of a site-2 protease family intramembrane metalloprotease. Science 318(5856):1608–1612PubMedGoogle Scholar
  93. 93.
    Koide K, Maegawa S, Ito K, Akiyama Y (2007) Environment of the active site region of RseP, an Escherichia coli regulated intramembrane proteolysis protease, assessed by site-directed cysteine alkylation. J Biol Chem 282(7):4553–4560PubMedGoogle Scholar
  94. 94.
    Akiyama Y, Kanehara K, Ito K (2004) RseP (YaeL), an Escherichia coli RIP protease, cleaves transmembrane sequences. EMBO J 23(22):4434–4442PubMedGoogle Scholar
  95. 95.
    Saito A, Hizukuri Y, Matsuo E, Chiba S et al (2011) Post-liberation cleavage of signal peptides is catalyzed by the site-2 protease (S2P) in bacteria. Proc Natl Acad Sci U S A 108(33):13740–13745PubMedGoogle Scholar
  96. 96.
    Shah S, Lee SF, Tabuchi K, Hao YH et al (2005) Nicastrin functions as a gamma-secretase-substrate receptor. Cell 122(3):435–447PubMedGoogle Scholar
  97. 97.
    Gur E, Ottofuelling R, Dougan DA (2013) Machines of destruction – AAA+  proteases and the adaptors that control them. In: Dougan DA (ed) Regulated proteolysis: from bacteria to yeast. Springer, Subcell Biochem 66:3–33Google Scholar
  98. 98.
    Cezairliyan BO, Sauer RT (2009) Control of Pseudomonas aeruginosa AlgW protease cleavage of MucA by peptide signals and MucB. Mol Microbiol 72(2):368–379PubMedGoogle Scholar
  99. 99.
    Martin DW, Holloway BW, Deretic V (1993) Characterization of a locus determining the mucoid status of Pseudomonas aeruginosa: AlgU shows sequence similarities with a Bacillus sigma factor. J Bacteriol 175(4):1153–1164PubMedGoogle Scholar
  100. 100.
    Schurr MJ, Yu H, Martinez-Salazar JM, Boucher JC et al (1996) Control of AlgU, a member of the sigma E-like family of stress sigma factors, by the negative regulators MucA and MucB and Pseudomonas aeruginosa conversion to mucoidy in cystic fibrosis. J Bacteriol 178(16):4997–5004PubMedGoogle Scholar
  101. 101.
    Qiu D, Eisinger VM, Rowen DW, Yu HD (2007) Regulated proteolysis controls mucoid conversion in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 104(19):8107–8112PubMedGoogle Scholar
  102. 102.
    Wood LF, Leech AJ, Ohman DE (2006) Cell wall-inhibitory antibiotics activate the alginate biosynthesis operon in Pseudomonas aeruginosa: roles of sigma (AlgT) and the AlgW and Prc proteases. Mol Microbiol 62(2):412–426PubMedGoogle Scholar
  103. 103.
    Qiu D, Eisinger VM, Head NE, Pier GB et al (2008) ClpXP proteases positively regulate alginate overexpression and mucoid conversion in Pseudomonas aeruginosa. Microbiology 154(Pt 7):2119–2130PubMedGoogle Scholar
  104. 104.
    Kim DY, Kim DR, Ha SC, Lokanath NK et al (2003) Crystal structure of the protease domain of a heat-shock protein HtrA from Thermotoga maritima. J Biol Chem 278(8):6543–6551PubMedGoogle Scholar
  105. 105.
    Cao M, Wang T, Ye R, Helmann JD (2002) Antibiotics that inhibit cell wall biosynthesis induce expression of the Bacillus subtilis sigmaW and sigmaM regulons. Mol Microbiol 45(5):1267–1276PubMedGoogle Scholar
  106. 106.
    Wiegert T, Homuth G, Versteeg S, Schumann W (2001) Alkaline shock induces the Bacillus subtilis sigma(W) regulon. Mol Microbiol 41(1):59–71PubMedGoogle Scholar
  107. 107.
    Schöbel S, Zellmeier S, Schumann W, Wiegert T (2004) The Bacillus subtilis sigmaW anti-sigma factor RsiW is degraded by intramembrane proteolysis through YluC. Mol Microbiol 52(4):1091–1105PubMedGoogle Scholar
  108. 108.
    Ellermeier CD, Losick R (2006) Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis. Genes Dev 20(14):1911–1922PubMedGoogle Scholar
  109. 109.
    Heinrich J, Wiegert T (2006) YpdC determines site-1 degradation in regulated intramembrane proteolysis of the RsiW anti-sigma factor of Bacillus subtilis. Mol Microbiol 62(2):566–579PubMedGoogle Scholar
  110. 110.
    Heinrich J, Hein K, Wiegert T (2009) Two proteolytic modules are involved in regulated intramembrane proteolysis of Bacillus subtilis RsiW. Mol Microbiol 74(6):1412–1426PubMedGoogle Scholar
  111. 111.
    Zellmeier S, Schumann W, Wiegert T (2006) Involvement of Clp protease activity in modulating the Bacillus subtilissigmaw stress response. Mol Microbiol 61(6):1569–1582PubMedGoogle Scholar
  112. 112.
    Makinoshima H, Glickman MS (2005) Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysis. Nature 436(7049):406–409PubMedGoogle Scholar
  113. 113.
    Sklar JG, Makinoshima H, Schneider JS, Glickman MS (2010) M. tuberculosis intramembrane protease Rip1 controls transcription through three anti-sigma factor substrates. Mol Microbiol 77(3):605–617PubMedGoogle Scholar
  114. 114.
    Hizukuri Y, Akiyama Y (2012) PDZ domains of RseP are not essential for sequential cleavage of RseA or stress-induced σE activation in vivo. Mol Microbiol 86(5):1232–1245Google Scholar

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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Graduate Program in BMMB, Department of Biochemistry and Molecular BiologyThe Pennsylvania State UniversityUniversity ParkUSA
  2. 2.Department of Biochemistry and Molecular BiologyThe Pennsylvania State UniversityUniversity ParkUSA

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