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

Authors:

Natalie K. Jones1,2,4,#, Nagla T.T. Arab1,3,#, Rawan Eid1,3,#, Nada Gharib1,5, Sara Sheibani1,2,6, Hojatollah Vali2, Chamel Khoury1, Alistair Murray1,2, Eric Boucher2, Craig A. Mandato2, Paul G. Young3 and Michael T. Greenwood1

doi: 10.15698/mic2015.07.213
Volume 2, pp. 247 to 255, published 06/07/2015.

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Affiliations:

1 Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.

2 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

3 Department of Biology, Queen’s University, Kingston, Ontario, Canada.

4 Present address: Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada.

5 Present address: Department of Biomedical Sciences, Queen’s University, Kingston, Ontario, Canada.

6 Present address: Defence Research and Development Canada, Alberta, Canada.

# These authors contributed equally.

Keywords: 

TC-1, apoptosis, cell death, anti-apoptotic, cell survival, cancer, yeast

Corresponding Author(s):

Michael T. Greenwood, Royal Military College of Canada, Department of Chemistry and Chemical Engineering, PO Box 17000 Station Forces; Kingston, Ontario, Canada, K7K 7B4 michael.greenwood@rmc.ca

Conflict of interest statement:

The authors declare there is no conflict of interest.

Please cite this article as:

Natalie K. Jones, Nagla T.T. Arab, Rawan Eid, Nada Gharib, Sara Sheibani, Hojatollah Vali, Chamel Khoury, Alistair Murray, Eric Boucher, Craig A. Mandato, Paul G. Young and Michael T. Greenwood (2015). Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast. Microbial Cell 2(7): 247-255.

© 2015 Jones et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

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.