The prodomain of Ssy5 protease controls receptor-activated proteolysis of transcription factor Stp1
2010 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 30, no 13, 3299-309 p.Article in journal (Refereed) Published
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
Place, publisher, year, edition, pages
2010. Vol. 30, no 13, 3299-309 p.
Research subject Cell Biology
IdentifiersURN: urn:nbn:se:su:diva-44307DOI: 10.1128/MCB.00323-10ISI: 000278626100013PubMedID: 20421414OAI: oai:DiVA.org:su-44307DiVA: diva2:360941