The Saccharomyces cerevisiae SOP1 and SOP2 genes, which act in cation homeostasis, can be functionally substituted by the Drosophila lethal(2)giant larvae tumor suppressor gene

By complementation of a salt-sensitive mutant of Saccharomyces cerevisiae, we cloned the SOP1 gene, encoding a 114.5-kDa protein of 1033 amino acids. Cells deleted for SOP1 exhibited sensitivity to sodium stress, but showed n o sensitivity to general osmotic stress. Following exposure of sop1 Delta c ells to NaCl stress, the intracellular Na+ level and the Na+/K+ ratio rose to values significantly higher than in wild type cells. Deletion of SOP2, e ncoding a protein sharing 54% amino acid identity with Sop1p, produced only slight Na+ sensitivity. Cells carrying a sop1 Delta sop2 Delta double dele tion became, however, hypersensitive to Na+ and exhibited increased sensiti vity also to Li+ and K+, suggesting involvement of both SOP1 and SOP2 in ca tion homeostasis. The predicted amino acid sequences of Sop1p and Sop2p sho w significant homologies with the cytoskeletal-associated protein encoded b y the Drosophila Lethal(2)giant larvae tumor suppressor gene. Immunolocaliz ation of Sop1p revealed a cytoplasmic distribution and cell fractionation s tudies showed that a significant fraction of Sop1p was recovered in a sedim entable fraction of the cytosolic material. Expression of a Drosophila l(2) gl cDNA in the sop1 Delta sop2 Delta strain partially restored the Na+ tole rance of the cells, indicating a functional relationship between the Sop pr oteins and the tumor suppressor protein, and a novel function in cell homeo stasis for this family of proteins extending from yeast to human.