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人甲状腺癌-1(TC-1)是一种脊椎动物特异性致癌蛋白,可保护酵母免受铜和促凋亡基因的影响。

Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast.

作者信息

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

机构信息

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.

出版信息

Microb Cell. 2015 Jul 6;2(7):247-255. doi: 10.15698/mic2015.07.213.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07bc/5349172/9894d29790ae/mic-02-247-g01.jpg

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