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

Natalie K Jones; Nagla T Arab; Rawan Eid; Nada Gharib; Sara Sheibani; Hojatollah Vali; Chamel Khoury; Alistair Murray; Eric Boucher; Craig A Mandato; Paul G Young; Michael T Greenwood

doi:10.15698/mic2015.07.213

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

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

Authors

Affiliations

¹ 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.
² Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada. ; Department of Biology, Queen's University, Kingston, Ontario, Canada.
³ Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada. ; Present address: Department of Biomedical Sciences, Queen's University, Kingston, Ontario, Canada.
⁴ 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: Defence Research and Development Canada, Alberta, Canada.
⁵ Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
⁶ Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.
⁷ 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.
⁸ Department of Biology, Queen's University, Kingston, Ontario, Canada.

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 YCA1, YBH3, NUC1, and AIF1. Even though the protective effects were more pronounced with the over-expression of YBH3 and YCA1, hTC-1 could still protect yeast mutants lacking YBH3 and YCA1 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.

Keywords: TC-1; anti-apoptotic; apoptosis; cancer; cell death; cell survival; yeast.

Grants and funding

We thank F. Madeo for plasmids. This work was supported by grants from NSERC and the Canadian Defense Academy to MTG. RW is the recipient of scholarship from Ontario’s Ministry of Research and Innovation.