Disease relevance of ECs4838

• We have identified a putative CpxR consensus binding site that is found upstream of a number of other E. coli genes [1].
• Identification of CpxR as a positive regulator of icm and dot virulence genes of Legionella pneumophila [2].

High impact information on ECs4838

• In Escherichia coli, the two-component Cpx system comprising the CpxA sensor kinase and the CpxR response regulator modulates gene expression in response to a variety of stresses including membrane-protein damage, starvation, and high osmolarity [3].
• Taken together we conclude that the copper-responsive genes are organized into a hierarchy of the regulation network, forming at least four regulons, i.e. CueR, CusR, CpxR and YedW regulons [4].
• After induction of T4S genes by a nutritional upshift and assembly of functional DNA transporters encoded by plasmid R1-16, host cells activated the CpxAR envelope stress signaling system, as revealed by induction or repression of downstream targets of the CpxR response regulator [5].
• Subsequent genetic analysis revealed that this phenotype is dependent on phosphorylation of the response regulator CpxR and that activation of CpxA in wild-type cells results in similar regulation of porin expression [6].
• Negative regulation of DNA repair gene (ung) expression by the CpxR/CpxA two-component system in Escherichia coli K-12 and induction of mutations by increased expression of CpxR [7].

Chemical compound and disease context of ECs4838

• The copper stimulon in Escherichia coli consists of four regulons, the CueR-, CusS/CusR-, CpxA/CpxR-, and YedV/YedW regulons [8].

Biological context of ECs4838

• It is unclear whether CpxA* phenotypes are caused solely by hyperphosphorylation of CpxR [9].
• It appears that certain mutant sensor kinases (CpxA*) either exhibit hyperactivity on CpxR or extend their signalling activity to one or more noncognate response regulators involved in cell division [10].
• However, deletion of the cpxRA operon, encoding the sensor kinase and its cognate regulator CpxR, has no effect on division site biogenesis [10].
• After gel-shift and DNase I foot-printing analyses, a conserved tandem repeat of pentanucleotide sequence, GTAAA(N)(4-8)GTAAA, with a conserved A of 4-bp upstream of each pentamer, was identified to be the CpxR-binding site [8].

Anatomical context of ECs4838

• We further show that the expression of a putative protease, HtpX, in the plasma membrane, is under the control of CpxR [11].

Associations of ECs4838 with chemical compounds

• It is comprised of the histidine kinase CpxA and the response regulator CpxR [12].
• In vivo and in vitro characterization of maltose-binding-protein fusions between the wild-type CpxA and a representative cpx* mutant, CpxA101, showed that the mutant CpxA is altered in phosphotransfer reactions with CpxR [13].

References