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

Autor: 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
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Microbial Cell, Vol 2, Iss 7, Pp 247-255 (2015)
Druh dokumentu: article
ISSN: 2311-2638
DOI: 10.15698/mic2015.07.213
Popis: 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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