文章基本信息

标题：Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae
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作者：Mohammed A. S. Khan ; P. Boon Chock ; Earl R. Stadtman 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：48
页码：17326-17331
DOI：10.1073/pnas.0508120102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In our previous study, we established that inhibition of apoptosis by the general caspase inhibitor is associated with an increase in the level of oxidized proteins in a multicellular eukaryotic system. To gain further insight into a potential link between oxidative stress and apoptosis, we carried out studies with Saccharomyces cerevisiae, which contains a gene (YCA1) that encodes synthesis of metacaspase, a homologue of the mammalian caspase, and is known to play a crucial role in the regulation of yeast apoptosis. We show that upon exposure to H2O2, the accumulation of protein carbonyls is much greater in a {Delta}yca1 strain lacking the YCA1 gene than in the wild type and that apoptosis was abrogated in the {Delta}yca1 strain, whereas wild type underwent apoptosis as measured by externalization of phosphatidylserine and the display of TUNEL-positive nuclei. We also show that H2O2-mediated stress leads to up-regulation of the 20S proteasome and suppression of ubiquitinylation activities. These findings suggest that deletion of the apoptotic-related caspase-like gene leads to a large H2O2-dependent accumulation of oxidized proteins and up-regulation of 20S proteasome activity.
关键词：H2O2 ; metacaspase ; programmed cell death ; proteasome activity ; protein carbonyl