DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response.
All cells have stress response pathways that maintain homeostasis in each cellular compartment. In the Gram-negative bacterium Escherichia coli, the sigma(E) pathway responds to protein misfolding in the envelope. The stress signal is transduced across the inner membrane to the cytoplasm via the inner membrane protein RseA, the anti-sigma factor that inhibits the transcriptional activity of sigma(E). Stress-induced activation of the pathway requires the regulated proteolysis of RseA. In this report we show that RseA is degraded by sequential proteolytic events controlled by the inner membrane-anchored protease DegS and the membrane-embedded metalloprotease YaeL, an ortholog of mammalian Site-2 protease (S2P). This is consistent with the mechanism of activation of ATF6, the mammalian unfolded protein response transcription factor by Site-1 protease and S2P. Thus, mammalian and bacterial cells employ a conserved proteolytic mechanism to activate membrane-associated transcription factors that initiate intercompartmental cellular stress responses.
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143, USA.
Benjamin M
BM
Alba
Jennifer A
JA
Leeds
Christina
C
Onufryk
Chi Zen
CZ
Lu
Carol A
CA
Gross
D051702:Activating Transcription Factor 6; D001412:Bacillus subtilis / Q000201:enzymology / Q000378:metabolism; D001426:Bacterial Proteins / Q000502:physiology*; D001665:Binding Sites; D015153:Blotting, Western; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology*; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012808:Sigma Factor / Q000378:metabolism*; D013053:Spectrophotometry; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic; D001616:beta-Galactosidase / Q000378:metabolism
D051702:Activating Transcription Factor 6; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C066496:DegS protein, Bacteria; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C433802:RseA protein, E coli; D012808:Sigma Factor; D014157:Transcription Factors; C489349:degS protein, Escherichia coli; D001616:beta-Galactosidase; D010450:Endopeptidases; C440001:RseP protein, E coli