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FEMS Yeast Res. 2008 Jun;8(4):540-63. doi: 10.1111/j.1567-1364.2008.00367.x. Epub 2008 Mar 18.

A TSC22-like motif defines a novel antiapoptotic protein family.

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  • 1Department of Medicine, McGill University, Montreal, Quebec, Canada.

Abstract

The apoptotic programme is evolutionarily conserved between yeast and metazoan organisms. We have previously identified a number of mammalian cDNAs capable of suppressing the deleterious effects of Bax expression in yeast. We herein report that one such suppressor, named Tsc22((86)), represents the C-terminal 86 amino acids of the previously characterized leucine zipper (LZ) motif-containing transcriptional regulator Tsc22. Employing a genome-wide two-hybrid screen, functional genomics, and deletion mutagenesis approaches, we conclude that Tsc22((86))-mediated antiapoptosis is independent of the LZ motif and is likely independent of effects on gene transcription. Rather, a 16-residue sequence within the conserved 56-residue TSC22 domain is necessary for antiapoptosis. The presence of a similar sequence was used to predict an antiapoptotic role for two yeast proteins, Sno1p and Fyv10p. Overexpression and knock-out experiments were used to validate this prediction. These findings demonstrate the potential of studying heterologous proteins in yeast to uncover novel biological insights into the regulation of apoptosis.

PMID:
18355271
[PubMed - indexed for MEDLINE]
PMCID:
PMC2593406
Free PMC Article

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