A branched pathway governing the activation of a developmental transcription factor by regulated intramembrane proteolysis.
The proteolytic activation of the membrane-associated transcription factor pro-sigma(K) is controlled by a signal transduction pathway during sporulation in the bacterium Bacillus subtilis. The pro-sigma(K) processing enzyme SpoIVFB, a membrane-embedded metalloprotease, is held inactive by two other integral-membrane proteins, SpoIVFA and BofA. We demonstrate that the signaling protease SpoIVB (IVB) triggers pro-sigma(K) processing by cleaving the extracellular domain of the SpoIVFA regulator at multiple sites. In vitro, these cleavages do not disrupt the interactions between SpoIVFA, SpoIVFB, and BofA, suggesting that IVB-dependent activation of the processing enzyme results from a conformational change in this complex. Our data further suggest that when IVB is unable to cleave SpoIVFA, it can still activate pro-sigma(K) processing through a second protease, CtpB. Finally, we demonstrate that CtpB, like IVB, triggers pro-sigma(K) processing by cleaving SpoIVFA. We propose that IVB regulates intramembrane proteolysis through two proteolytic pathways, both of which converge on the same regulator.
Campo
Nathalie
N
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
Rudner
David Z
DZ
D001412:Bacillus subtilis / Q000166:cytology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013171:Spores, Bacterial / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
D001426:Bacterial Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C112176:pro-sigmaK protein, Bacillus subtilis; C074423:bofA protein, Bacillus subtilis; C071441:spoIVFA protein, Bacillus subtilis; D010450:Endopeptidases; D010447:Peptide Hydrolases; C071442:spoIVFB protein, Bacillus subtilis