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

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...

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Main Authors: Natalie K. Jones, Nagla T.T. Arab, Rawan Eid, Nada Gharib, Sara Sheiban, Hojatollah Vali, Chamel Khoury, Alistair Murray, Eric Boucher, Craig A. Mandato, Paul G. Young, Michael T. Greenwood
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Language:English
Published: Shared Science Publishers OG 2015-07-01
Series:Microbial Cell
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Online Access:http://microbialcell.com/researcharticles/human-thyroid-cancer-1-tc-1-is-a-vertebrate-specific-oncogenic-protein-that-protects-against-copper-and-pro-apoptotic-genes-in-yeast/
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author Natalie K. Jones
Nagla T.T. Arab
Rawan Eid
Nada Gharib
Sara Sheiban
Hojatollah Vali
Chamel Khoury
Alistair Murray
Eric Boucher
Craig A. Mandato
Paul G. Young
Michael T. Greenwood
author_facet Natalie K. Jones
Nagla T.T. Arab
Rawan Eid
Nada Gharib
Sara Sheiban
Hojatollah Vali
Chamel Khoury
Alistair Murray
Eric Boucher
Craig A. Mandato
Paul G. Young
Michael T. Greenwood
author_sort Natalie K. Jones
collection DOAJ
description 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.
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spelling doaj-art-47f042867bfa408ba5fcd07f9692b5072025-08-20T02:52:37ZengShared Science Publishers OGMicrobial Cell2311-26382015-07-012724725510.15698/mic2015.07.213123455678Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeastNatalie K. Jones0Nagla T.T. Arab1Rawan Eid2Nada Gharib3Sara Sheiban4Hojatollah Vali5Chamel Khoury6Alistair Murray7Eric Boucher8Craig A. Mandato9Paul G. Young10Michael T. Greenwood11Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.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.Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.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.Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.Department of Biology, Queen’s University, Kingston, Ontario, Canada.Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario, Canada.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.http://microbialcell.com/researcharticles/human-thyroid-cancer-1-tc-1-is-a-vertebrate-specific-oncogenic-protein-that-protects-against-copper-and-pro-apoptotic-genes-in-yeast/TC-1apoptosiscell deathanti-apoptoticcell survivalcanceryeast
spellingShingle Natalie K. Jones
Nagla T.T. Arab
Rawan Eid
Nada Gharib
Sara Sheiban
Hojatollah Vali
Chamel Khoury
Alistair Murray
Eric Boucher
Craig A. Mandato
Paul G. Young
Michael T. Greenwood
Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast
Microbial Cell
TC-1
apoptosis
cell death
anti-apoptotic
cell survival
cancer
yeast
title Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast
title_full Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast
title_fullStr Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast
title_full_unstemmed Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast
title_short Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast
title_sort human thyroid cancer 1 tc 1 is a vertebrate specific oncogenic protein that protects against copper and pro apoptotic genes in yeast
topic TC-1
apoptosis
cell death
anti-apoptotic
cell survival
cancer
yeast
url http://microbialcell.com/researcharticles/human-thyroid-cancer-1-tc-1-is-a-vertebrate-specific-oncogenic-protein-that-protects-against-copper-and-pro-apoptotic-genes-in-yeast/
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