Madeo Frank, Herker Eva, Maldener Corinna, Wissing Silke, Lächelt Stephan, Herlan Mark, Fehr Markus, Lauber Kirsten, Sigrist Stephan J, Wesselborg Sebastian, Fröhlich Kai Uwe
Institute for Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany.
Mol Cell. 2002 Apr;9(4):911-7. doi: 10.1016/s1097-2765(02)00501-4.
Yeast can undergo cell death accompanied by cellular markers of apoptosis. However, orthologs of classical mammalian apoptosis regulators appeared to be missing from the yeast genome, challenging a common mechanism of yeast and mammalian apoptosis. Here we investigate Yor197w, a yeast protein with structural homology to mammalian caspases, and demonstrate caspase-like processing of the protein. Hydrogen peroxide treatment induces apoptosis together with a caspase-like enzymatic activity in yeast. This response is completely abrogated after disruption and strongly stimulated after overexpression of Yor197w. Yor197w also mediates the death process within chronologically aged cultures, pointing to a physiological role in elimination of overaged cells. We conclude that Yor197w indeed functions as a bona fide caspase in yeast and propose the name Yeast Caspase-1 (YCA1, gene YCA1).
酵母可经历伴随细胞凋亡细胞标志物的细胞死亡。然而,酵母基因组中似乎缺少经典哺乳动物凋亡调节因子的直系同源物,这对酵母和哺乳动物凋亡的共同机制提出了挑战。在此,我们研究了Yor197w,一种与哺乳动物半胱天冬酶具有结构同源性的酵母蛋白,并证明了该蛋白的类半胱天冬酶加工过程。过氧化氢处理可诱导酵母细胞凋亡并伴有类半胱天冬酶活性。在Yor197w基因破坏后,这种反应完全消失,而在其过表达后则受到强烈刺激。Yor197w还介导了时序老化培养物中的死亡过程,表明其在清除老化细胞中具有生理作用。我们得出结论,Yor197w在酵母中确实作为一种真正的半胱天冬酶发挥作用,并提议将其命名为酵母半胱天冬酶-1(YCA1,基因YCA1)。