The prodomain of Ssy5 protease controls receptor-activated proteolysis of transcription factor Stp1.

Stockholm University, Wenner-Gren Institute, S-106 91 Stockholm, Sweden.
Extracellular amino acids induce the yeast SPS sensor to endoproteolytically cleave transcription factors Stp1 and Stp2 in a process termed receptor-activated proteolysis (RAP). Ssy5, the activating endoprotease, is synthesized with a large N-terminal prodomain and a C-terminal chymotrypsin-like catalytic (Cat) domain. During biogenesis, Ssy5 cleaves itself and the prodomain and Cat domain remain associated, forming an inactive primed protease. Here we show that the prodomain is a potent inhibitor of Cat domain activity and that its inactivation is a requisite for RAP. Accordingly, amino acid-induced signals trigger proteasome-dependent degradation of the prodomain. A mutation that stabilizes the prodomain prevents Stp1 processing, whereas destabilizing mutations lead to constitutive RAP-independent Stp1 processing. We fused a conditional degron to the prodomain to synthetically reprogram the amino acid-responsive SPS signaling pathway, placing it under temperature control. Our results define a regulatory mechanism that is novel for eukaryotic proteases functioning within cells.
Mesh Terms:
Endopeptidases, Mutation, Nuclear Proteins, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, RNA-Binding Proteins, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Serine Proteases, Signal Transduction, Transcription Factors
Mol. Cell. Biol. Jul. 01, 2010; 30(13);3299-309 [PUBMED:20421414]
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