Disruption of protein-protein interaction in the Mgl-1 oncoprotein.
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, DeltaG450 and DeltaD453, 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.
Kim
Yong-Soo
YS
Cell and Gene Therapy Research Institute, Graduate School of Life Science and Biotechnology, Pochon CHA University, CHA General Hospital, Seoul 135-081, Korea.
Kim
Yu-Kyung
YK
Park
Jung-Mi
JM
Han
In-Soo
IS
Ajjappala
Brijesh S
BS
Kang
Incheol
I
Baek
Kwang-Hyun
KH
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001212:Asialoglycoproteins / Q000737:chemistry* / Q000502:physiology*; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D017353:Gene Deletion; D005816:Genetic Complementation Test; D037181:Lectins, C-Type / Q000737:chemistry* / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D018076:DNA, Complementary; D037181:Lectins, C-Type; D008565:Membrane Proteins