文章基本信息

标题：Modulation of mammalian cell growth and death by prokaryotic and eukaryotic cytochrome c
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作者：Yoshinori Hiraoka ; Tohru Yamada ; Masatoshi Goto 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：2004
卷号：101
期号：17
页码：6427-6432
DOI：10.1073/pnas.0401631101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cytochrome c551, an 8,685-Da haem-containing protein, is known to be involved in electron transfer during dissimilative denitrification by Pseudomonas aeruginosa. Both cytochrome c551 and copper-containing redox protein azurin have been used in vitro as partners in electron transfer. Azurin has been reported to induce apoptosis in macrophages and cancer cells. We now report that, unlike azurin, cytochrome c551, termed Cyt c551, has very little ability to induce apoptosis in J774 cell line-derived macrophages but demonstrates significant inhibition of cell cycle progression in such cells. A mutant form of Cyt c551, V23DI59E, has significantly reduced ability to inhibit cell cycle progression but demonstrates a higher level of apoptosis-inducing activity in macrophages, compared with WT Cyt c551. Interestingly, the WT Cyt c551, but not the mutant form, significantly enhances the level of tumor suppressor protein p16Ink4a, a known inhibitor of cell cycle progression whereas the mutant form seems to form a complex with tumor suppressor protein p53, thereby enhancing its intracellular level to some extent. Eukaryotic cytochromes such as horse and bovine cytochrome c have also been shown to induce apoptosis but not inhibition of cell cycle progression in J774 cells, thus signifying a role of this redox protein in entry to, and in the induction of, cell death in mammalian cells.