DegS and YaeL participate sequentially in the cleavage of RseA to activate the ςE-dependent extracytoplasmic stress response
- Benjamin M. Alba1,5,
- Jennifer A. Leeds4,5,6,
- Christina Onufryk1,
- Chi Zen Lu3, and
- Carol A. Gross2,3,7
- 1Department of Biochemistry and Biophysics, 2Department of Microbiology and Immunology, and 3Department of Stomatology, University of California at San Francisco, San Francisco, California 94143, USA; 4Harvard Medical School, Department of Microbiology and Molecular Genetics, Boston, Massachusetts 02115, USA
Abstract
All cells have stress response pathways that maintain homeostasis in each cellular compartment. In the Gram-negative bacteriumEscherichia coli, the ςE 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 ςE. 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.
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Footnotes
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↵5 These authors contributed equally to this work.
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↵6 Present address: Dyax Corp., 300 Technology Square, Cambridge, MA 02139, USA.
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↵7 Corresponding author.
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E-MAIL cgross{at}cgl.ucsf.edu; FAX (415) 476-4204.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1008902.
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- Received May 20, 2002.
- Accepted June 21, 2002.
- Cold Spring Harbor Laboratory Press
