Jones Natalie K, Arab Nagla T, Eid Rawan, Gharib Nada, Sheibani Sara, Vali Hojatollah, Khoury Chamel, Murray Alistair, Boucher Eric, Mandato Craig A, Young Paul G, Greenwood Michael T
Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada. ; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. ; Present address: Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada. ; Department of Biology, Queen's University, Kingston, Ontario, Canada.
Microb Cell. 2015 Jul 6;2(7):247-255. doi: 10.15698/mic2015.07.213.
The human Thyroid Cancer-1 (hTC-1) protein, also known as C8orf4 was initially identified as a gene that was up-regulated in human thyroid cancer. Here we show that hTC-1 is a peptide that prevents the effects of over-expressing Bax in yeast. Analysis of the 106 residues of hTC-1 in available protein databases revealed direct orthologues in jawed-vertebrates, including mammals, frogs, fish and sharks. No TC-1 orthologue was detected in lower organisms, including yeast. Here we show that TC-1 is a general pro-survival peptide since it prevents the growth- and cell death-inducing effects of copper in yeast. Human TC-1 also prevented the deleterious effects that occur due to the over-expression of a number of key pro-apoptotic peptides, including , , , and . Even though the protective effects were more pronounced with the over-expression of and , hTC-1 could still protect yeast mutants lacking and from the effects of copper sulfate. This suggests that the protective effects of TC-1 are not limited to specific pathways or processes. Taken together, our results indicate that hTC-1 is a pro-survival protein that retains its function when heterologously expressed in yeast. Thus yeast is a useful model to characterize the potential roles in cell death and survival of cancer related genes.
人类甲状腺癌-1（hTC-1）蛋白，也被称为C8orf4，最初被鉴定为在人类甲状腺癌中上调的基因。在此我们表明，hTC-1是一种能阻止酵母中过表达Bax产生效应的肽。在现有的蛋白质数据库中对hTC-1的106个残基进行分析，发现有颌脊椎动物（包括哺乳动物、青蛙、鱼类和鲨鱼）中存在直系同源物。在包括酵母在内的低等生物中未检测到TC-1直系同源物。在此我们表明，TC-1是一种普遍的促生存肽，因为它能阻止酵母中铜诱导的生长和细胞死亡效应。人类TC-1还能阻止由于多种关键促凋亡肽（包括 、 、 和 ）过表达而产生的有害效应。尽管 和 过表达时保护作用更明显，但hTC-1仍能保护缺乏 和 的酵母突变体免受硫酸铜的影响。这表明TC-1的保护作用不限于特定途径或过程。综上所述，我们的结果表明hTC-1是一种促生存蛋白，在酵母中异源表达时仍保留其功能。因此，酵母是表征癌症相关基因在细胞死亡和生存中潜在作用的有用模型。
