A TSC22-like motif defines a novel antiapoptotic protein family

Chamel M Khoury1, Zhao Yang, Xiao Yu Li

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

FEMS Yeast Research
|March 22, 2008
PubMed

Insights

Researchers found that a specific part of the Tsc22 protein, Tsc22((86)), can prevent programmed cell death (apoptosis) in yeast. This anti-apoptotic function is independent of gene transcription and relies on a small sequence within the TSC22 domain.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Programmed cell death (apoptosis) is a fundamental biological process conserved across species, from yeast to metazoans.
  • Mammalian cDNAs have been identified that can suppress the detrimental effects of Bax protein expression in yeast.

Purpose of the Study:

  • To investigate the mechanism by which Tsc22((86)), a C-terminal fragment of the Tsc22 transcriptional regulator, mediates anti-apoptotic effects in yeast.
  • To identify the specific protein domains or sequences responsible for the anti-apoptotic activity of Tsc22((86)).

Main Methods:

  • Genome-wide two-hybrid screening
  • Functional genomics assays
  • Deletion mutagenesis
  • Overexpression and knock-out experiments in yeast

Main Results:

  • Tsc22((86)) suppresses Bax-induced apoptosis in yeast independently of its leucine zipper motif and gene transcription.
  • A 16-residue sequence within the conserved 56-residue TSC22 domain is essential for the anti-apoptotic activity of Tsc22((86)).
  • The identified sequence motif predicted and was validated for an anti-apoptotic role in yeast proteins Sno1p and Fyv10p.

Conclusions:

  • The anti-apoptotic function of Tsc22((86)) is mediated by a specific sequence within the TSC22 domain, not by transcriptional regulation.
  • Studying heterologous proteins in yeast can reveal novel insights into the conserved mechanisms regulating apoptosis.

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