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KMID : 0545120170270030633
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Journal of Microbiology and Biotechnology
2017 Volume.27 No. 3 p.633 ~ p.643
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Pro-Apoptotic Role of the Human YPEL5 Gene Identified by Functional Complementation of a Yeast moh1Δ Mutation
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Lee Ji-Young
Jun Do-Youn
Park Ju-Eun
Kwon Gi-Hyun
Kim Jong-Sik
Kim Young-Ho
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Abstract
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To examine the pro-apoptotic role of the human ortholog (YPEL5) of the Drosophila Yippee protein, the cell viability of Saccharomyces cerevisiae mutant strain with deleted MOH1, the yeast ortholog, was compared with that of the wild-type (WT)-MOH1 strain after exposure to different apoptogenic stimulants, including UV irradiation, methyl methanesulfonate (MMS), camptothecin (CPT), heat shock, and hyperosmotic shock. The moh1Δ mutant exhibited enhanced cell viability compared with the WT-MOH1 strain when treated with lethal UV irradiation, 1.8 mM MMS, 100 μM CPT, heat shock at 50°C, or 1.2 M KCl. At the same time, the level of Moh1 protein was commonly up-regulated in the WT-MOH1 strain as was that of Ynk1 protein, which is known as a marker for DNA damage. Although the enhanced UV resistance of the moh1Δ mutant largely disappeared following transformation with the yeast MOH1 gene or one of the human YPEL1-YPEL5 genes, the transformant bearing pYES2- YPEL5 was more sensitive to lethal UV irradiation and its UV sensitivity was similar to that of the WT-MOH1 strain. Under these conditions, the UV irradiation-induced apoptotic events, such as FITC-Annexin V stainability, mitochondrial membrane potential (Δψm) loss, and metacaspase activation, occurred to a much lesser extent in the moh1Δ mutant compared with the WT-MOH1 strain and the mutant strain bearing pYES2-MOH1 or pYES2-YPEL5. These results demonstrate the functional conservation between yeast Moh1 and human YPEL5, and their involvement in mitochondria-dependent apoptosis induced by DNA damage.
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KEYWORD
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DNA damage, Drosophila Yippee, Apoptosis, metacaspase, S. cerevisiae MOH1, human YPEL5
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