PMID:12183369

Citation	Alba, BM, Leeds, JA, Onufryk, C, Lu, CZ and Gross, CA (2002) DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev. 16:2156-68
Abstract	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.
Links	PubMed PMC186436 Online version:10.1101/gad.1008902
Keywords	Activating Transcription Factor 6; Bacillus subtilis/enzymology; Bacillus subtilis/metabolism; Bacterial Proteins/physiology; Binding Sites; Blotting, Western; Cytoplasm/metabolism; DNA-Binding Proteins/metabolism; Endopeptidases/physiology; Endoplasmic Reticulum/metabolism; Escherichia coli/metabolism; Escherichia coli Proteins/physiology; Membrane Proteins/metabolism; Membrane Proteins/physiology; Mutation; Plasmids/metabolism; Protein Binding; Protein Structure, Tertiary; Sigma Factor/metabolism; Spectrophotometry; Subcellular Fractions/metabolism; Time Factors; Transcription Factors/metabolism; Transduction, Genetic; beta-Galactosidase/metabolism
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