Mammalian homologues of the Lethal giant larvae (Lgl) tumor suppressor gene have been identified and these homologues can complement the yeast double mutant of Sop1 and Sop2, the yeast homologue of Lgl, as reported previously. In the absence of these genes in yeast, cellular viability is affected at restrictive temperature and salt environments. Members of this family contain five or more of the WD-40 repeat motifs, which is known to be involved in protein-protein interaction. In order to investigate the biochemical roles for conserved amino acids within the most conserved WD-40 repeat motif amongst these family members, we generated deletion mutants for five conserved amino acids (G450, H451, D453, W459 and D460) in mouse Lgl-1 (Mgl-1), located between 450-460 amino acids. We found that the deletion mutants of Mgl-1, ΔG450 and ΔD453, were not capable of complementing yeast mutants of Sop1 and Sop2 at restrictive temperature and high salt environments. These results indicate that the WD-40 repeat motif is important for cellular viability by regulating temperature-sensitivity and salt tolerance in yeast.

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