info:eu-repo/semantics/article
DNA‐damage inducible protein 1 is a conserved metacaspase substrate that is cleaved and further destabilized in yeast under specific metabolic conditions
Fecha
2018-03Registro en:
Bouvier, León Alberto; Niemirowicz, Gabriela Teresa; Salas Sarduy, Emir; Cazzulo, Juan Jose; Alvarez, Vanina Eder; DNA‐damage inducible protein 1 is a conserved metacaspase substrate that is cleaved and further destabilized in yeast under specific metabolic conditions; Wiley Blackwell Publishing, Inc; Febs Journal; 285; 6; 3-2018; 1097-1110
1742-464X
CONICET Digital
CONICET
Autor
Bouvier, León Alberto
Niemirowicz, Gabriela Teresa
Salas Sarduy, Emir
Cazzulo, Juan Jose
Alvarez, Vanina Eder
Resumen
Metacaspases, distant relatives of metazoan caspases, have been shown to participate in programmed cell death in plants and in progression of the cell cycle and removal of protein aggregates in unicellular eukaryotes. However, since natural proteolytic substrates have scarcely been identified to date, their roles in these processes remain unclear. Here, we report that the DNA‐damage inducible protein 1 (Ddi1) represents a conserved protein substrate for metacaspases belonging to divergent unicellular eukaryotes (trypanosomes and yeasts). We show that although the recognized cleavage sequence is not identical among the different model organisms tested, in all of them the proteolysis consequence is the removal of the ubiquitin‐associated domain (UBA) present in the protein. We also demonstrate that Ddi1 cleavage is tightly regulated in vivo as it only takes place in yeast when calcium increases but under specific metabolic conditions. Finally, we show that metacaspase‐mediated Ddi1 cleavage reduces the stability of this protein which can certainly impact on the many functions ascribed for it, including shuttle to the proteasome, cell cycle control, late secretory pathway regulation, among others.