Wadskog Ingrid, Maldener Corinna, Proksch Astrid, Madeo Frank, Adler Lennart
Department of Cell and Molecular Biology/Microbiology, Göteborg University, SE-40530 Göteborg, Sweden.
Mol Biol Cell. 2004 Mar;15(3):1436-44. doi: 10.1091/mbc.e03-02-0114. Epub 2004 Jan 12.
Yeast cells deleted for the SRO7/SOP1 encoded tumor suppressor homologue show increased sensitivity to NaCl stress. On exposure to growth-inhibiting NaCl concentrations, sro7Delta mutants display a rapid loss in viability that is associated with markers of apoptosis: accumulation of reactive oxygen species, DNA breakage, and nuclear fragmentation. Additional deletion of the yeast metacaspase gene YCA1 prevents the primary fast drop in viability and diminishes nuclear fragmentation and DNA breakage. We also observed that NaCl induced loss in viability of wild-type cells is Yca1p dependent. However, a yeast strain deleted for both SRO7 and its homologue SRO77 exhibits NaCl-induced cell death that is independent on YCA1. Likewise, sro77Delta single mutants do not survive better after additional deletion of the YCA1 gene, and both sro77Delta and sro77Deltayca1Delta mutants display apoptotic characteristics when exposed to growth-inhibiting salinity, suggesting that yeast possesses Yca1p-independent pathway(s) for apoptosis-like cell death. The activity of Yca1p increases with increasing NaCl stress and sro7Delta mutants achieve levels that are higher than in wild-type cells. However, mutants lacking SRO77 do not enhance caspase activity when subject to NaCl stress, suggesting that Sro7p and Sro77p exert opposing effects on the cellular activity of Yca1p.
缺失SRO7/SOP1编码的肿瘤抑制同源物的酵母细胞对NaCl胁迫的敏感性增加。在暴露于抑制生长的NaCl浓度时，sro7Delta突变体显示出活力的快速丧失，这与凋亡标记相关：活性氧的积累、DNA断裂和核碎片化。酵母metacaspase基因YCA1的额外缺失可防止活力的主要快速下降，并减少核碎片化和DNA断裂。我们还观察到，NaCl诱导的野生型细胞活力丧失依赖于Yca1p。然而，同时缺失SRO7及其同源物SRO77的酵母菌株表现出与YCA1无关的NaCl诱导的细胞死亡。同样，YCA1基因额外缺失后，sro77Delta单突变体的存活情况并未改善，并且sro77Delta和sro77Deltayca1Delta突变体在暴露于抑制生长的盐度时均表现出凋亡特征，这表明酵母具有与Yca1p无关的凋亡样细胞死亡途径。Yca1p的活性随着NaCl胁迫的增加而增加，并且sro7Delta突变体达到的水平高于野生型细胞。然而，缺乏SRO77的突变体在受到NaCl胁迫时不会增强caspase活性，这表明Sro7p和Sro77p对Yca1p的细胞活性发挥相反的作用。
