title: Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast.
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, includingYCA1,YBH3,NUC1, andAIF1. Even though the protective effects were more pronounced with the over-expression ofYBH3andYCA1, hTC-1 could still protect yeast mutants lackingYBH3andYCA1from 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.
authors.affiliation: 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.
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Jones
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada. ; Department of Biology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Nagla T
authors.initials: NT
authors.lastname: Arab
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada. ; Department of Biology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Rawan
authors.initials: R
authors.lastname: Eid
authors.affiliation: 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.
authors.forename: Nada
authors.initials: N
authors.lastname: Gharib
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Sheibani
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Hojatollah
authors.initials: H
authors.lastname: Vali
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.
authors.forename: Chamel
authors.initials: C
authors.lastname: Khoury
authors.affiliation: 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.
authors.forename: Alistair
authors.initials: A
authors.lastname: Murray
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Boucher
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Mandato
authors.affiliation: Department of Biology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Young
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Greenwood
keywords: TC-1; anti-apoptotic; apoptosis; cancer; cell death; cell survival; yeast