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Gene Review

degP  -  serine endoprotease (protease Do),...

Escherichia coli str. K-12 substr. MG1655

 
 
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Disease relevance of degP

  • The influence of extracytoplasmic proteases on the resistance of Escherichia coli to the antimicrobial peptide protamine was investigated by testing strains with deletions in the protease genes degP, ptr, and ompT [1].
  • A degP mutant of Shigella flexneri was identified in a screen for insertion mutants that invaded cultured cells but did not form wild-type plaques in monolayers [2].
  • Two independent insertions in the ygdP open reading frame relieve the toxicity of the fusion protein and share two additional properties with prlF1: cold sensitivity and the ability to suppress the temperature sensitivity of a degP null mutation [3].
  • A degP (htrA)-like gene of Bradyrhizobium japonicum was identified immediately downstream of two genes (hspB and hspC) coding for small heat-shock proteins [4].
  • Mutations in the htrA genes of Salmonella, Brucella and Yersinia cause decreased survival in mice and/or macrophages, and htrA mutants can act as vaccines, as cloning hosts and as carriers of heterologous antigens [5].
 

High impact information on degP

  • The extent of degP expression caused by NlpE overproduction was dependent on the mode of degP-lacZ fusion [6].
  • On the other hand, new inner membrane lipoprotein YafY strongly induced degP expression irrespective of the mode of fusion even though the level of overproduced YafY was lower than that of NlpE [6].
  • The degP gene encodes a periplasmic protease, which is thought to be involved in the digestion of unfolded proteins, and is essential for growth at high temperatures [6].
  • In E. coli, a functional htrA gene product is required for cell survival after heat shock or oxidative stress; its role appears to be the degradation of denatured proteins [7].
  • While a functional degP gene is required for full cpxA*-mediated suppression of both toxic envelope proteins, residual suppression is seen in cpxA* degP::Tn10 double mutants [8].
 

Chemical compound and disease context of degP

 

Biological context of degP

 

Anatomical context of degP

  • The degP mutant SM1100 invaded Henle cells at wild-type levels and induced apoptosis in macrophages but formed smaller plaques than those formed by wild-type S. flexneri in confluent monolayers of Henle and Caco-2 cells [2].
  • Deletion of the htrA gene in strain LF82 induced increased sensitivity of the isogenic mutant to oxidative stress caused by hydrogen peroxide and a reduced rate of growth in an acid and nutrient-poor medium partly reproducing the microenvironment of the phagosome [12].
  • Both systems overlap in the transcriptional regulation of the htrA gene encoding a protease that degrades misfolded proteins in the periplasm [13].
 

Associations of degP with chemical compounds

  • However, inactivation of the nlpE gene or mutations eliminating the ability to make acetyl phosphate did not alter the high level of degP expression in pss-93 mutants [14].
 

Regulatory relationships of degP

  • The arabinose-inducibility was also investigated in the expression system with the coexistence of the trc promoter system regulating pac expression and another arabinose-inducible promoter system of araB regulating degP coexpression [15].
 

Other interactions of degP

  • A mutant of degQ, a close homolog of degP, was not attenuated in mice [10].
  • Through this approach, we identified null mutations in the wecE, rmlAECA, and wecF loci that increase degP transcription [9].
  • Similarly, extracts from degP- and ompT-deleted mutants were able to significantly stabilize in vitro-synthesized PLD, which otherwise disappeared within 30 min [16].
  • Alteration of the lipoprotein-sorting signals of NlpE and YafY did not abolish the degP induction [6].
  • These results suggest that the absence of OMPLA corrects the degP temperature-sensitive phenotype by inducing the Cpx and sigma(E) regulons rather than by inactivating the phospholipase per se [17].
 

Analytical, diagnostic and therapeutic context of degP

  • Site-directed mutagenesis was performed on the htrA gene to ablate the endogenous serine protease activity of wild-type HtrA, and it was found that eight of nine recombinant mutant proteins had no measurable residual proteolytic activity [18].
  • When the putative htrA gene was amplified by polymerase chain reaction and used as template for in vitro transcription and translation, a protein with an apparent molecular mass of 62 kDa was synthesized from the plasmid template [19].

References

  1. Identification of OmpT as the protease that hydrolyzes the antimicrobial peptide protamine before it enters growing cells of Escherichia coli. Stumpe, S., Schmid, R., Stephens, D.L., Georgiou, G., Bakker, E.P. J. Bacteriol. (1998) [Pubmed]
  2. Shigella flexneri DegP facilitates IcsA surface expression and is required for efficient intercellular spread. Purdy, G.E., Hong, M., Payne, S.M. Infect. Immun. (2002) [Pubmed]
  3. Null mutations in a Nudix gene, ygdP, implicate an alarmone response in a novel suppression of hybrid jamming. Hand, N.J., Silhavy, T.J. J. Bacteriol. (2003) [Pubmed]
  4. Identification of the Bradyrhizobium japonicum degP gene as part of an operon containing small heat-shock protein genes. Narberhaus, F., Weiglhofer, W., Fischer, H.M., Hennecke, H. Arch. Microbiol. (1998) [Pubmed]
  5. The HtrA family of serine proteases. Pallen, M.J., Wren, B.W. Mol. Microbiol. (1997) [Pubmed]
  6. Effects of lipoprotein overproduction on the induction of DegP (HtrA) involved in quality control in the Escherichia coli periplasm. Miyadai, H., Tanaka-Masuda, K., Matsuyama, S., Tokuda, H. J. Biol. Chem. (2004) [Pubmed]
  7. Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage. Hu, S.I., Carozza, M., Klein, M., Nantermet, P., Luk, D., Crowl, R.M. J. Biol. Chem. (1998) [Pubmed]
  8. Mutational activation of the Cpx signal transduction pathway of Escherichia coli suppresses the toxicity conferred by certain envelope-associated stresses. Cosma, C.L., Danese, P.N., Carlson, J.H., Silhavy, T.J., Snyder, W.B. Mol. Microbiol. (1995) [Pubmed]
  9. Accumulation of the enterobacterial common antigen lipid II biosynthetic intermediate stimulates degP transcription in Escherichia coli. Danese, P.N., Oliver, G.R., Barr, K., Bowman, G.D., Rick, P.D., Silhavy, T.J. J. Bacteriol. (1998) [Pubmed]
  10. Role of sigma E-regulated genes in Escherichia coli uropathogenesis. Redford, P., Welch, R.A. Infect. Immun. (2006) [Pubmed]
  11. Adenylate cyclase mutations rescue the degP temperature-sensitive phenotype and induce the sigma E and Cpx extracytoplasmic stress regulons in Escherichia coli. Strozen, T.G., Langen, G.R., Howard, S.P. J. Bacteriol. (2005) [Pubmed]
  12. HtrA stress protein is involved in intramacrophagic replication of adherent and invasive Escherichia coli strain LF82 isolated from a patient with Crohn's disease. Bringer, M.A., Barnich, N., Glasser, A.L., Bardot, O., Darfeuille-Michaud, A. Infect. Immun. (2005) [Pubmed]
  13. Regulation of htrA expression in Yersinia enterocolitica. Heusipp, G., Nelson, K.M., Schmidt, M.A., Miller, V.L. FEMS Microbiol. Lett. (2004) [Pubmed]
  14. The Cpx two-component signal transduction pathway is activated in Escherichia coli mutant strains lacking phosphatidylethanolamine. Mileykovskaya, E., Dowhan, W. J. Bacteriol. (1997) [Pubmed]
  15. Arabinose-induction of lac-derived promoter systems for penicillin acylase production in Escherichia coli. Narayanan, N., Hsieh, M.Y., Xu, Y., Chou, C.P. Biotechnol. Prog. (2006) [Pubmed]
  16. Reduction of protein degradation by use of protease-deficient mutants in cell-free protein synthesis system of Escherichia coli. Jiang, X., Oohira, K., Iwasaki, Y., Nakano, H., Ichihara, S., Yamane, T. J. Biosci. Bioeng. (2002) [Pubmed]
  17. Absence of the outer membrane phospholipase A suppresses the temperature-sensitive phenotype of Escherichia coli degP mutants and induces the Cpx and sigma(E) extracytoplasmic stress responses. Langen, G.R., Harper, J.R., Silhavy, T.J., Howard, S.P. J. Bacteriol. (2001) [Pubmed]
  18. The Haemophilus influenzae HtrA protein is a protective antigen. Loosmore, S.M., Yang, Y.P., Oomen, R., Shortreed, J.M., Coleman, D.C., Klein, M.H. Infect. Immun. (1998) [Pubmed]
  19. Cloning, expression and sequence analysis of the Bartonella henselae gene encoding the HtrA stress-response protein. Anderson, B., Jones, D., Burgess, A. Gene (1996) [Pubmed]
 
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