Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show increased susceptibility to apoptosis-like cell death on exposure to NaCl stress.
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.
Wadskog
Ingrid
I
Department of Cell and Molecular Biology/Microbiology, Göteborg University, SE-40530 Göteborg, Sweden.
Maldener
Corinna
C
Proksch
Astrid
A
Madeo
Frank
F
Adler
Lennart
L
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000502:physiology; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012965:Sodium Chloride / Q000633:toxicity*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C116430:SRO7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012965:Sodium Chloride; D020169:Caspases; C456272:MCA1 protein, S cerevisiae