title: A TSC22-like motif defines a novel antiapoptotic protein family.
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.
authors: Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors: Chamel M
authors: CM
authors: Khoury
authors: Zhao
authors: Z
authors: Yang
authors: Xiao Yu
authors: XY
authors: Li
authors: Marissa
authors: M
authors: Vignali
authors: Stanley
authors: S
authors: Fields
authors: Michael T
authors: MT
authors: Greenwood
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D017353:Gene Deletion; D018628:Gene Dosage; D050296:Microbial Viability; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
chemical_list: D051017:Apoptosis Regulatory Proteins; D029701:Saccharomyces cerevisiae Proteins; C499441:Sno1 protein, S cerevisiae