salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines.
The number of cells in an organism is determined by regulating both cell proliferation and cell death. Relatively few mechanisms have been identified that can modulate both of these processes. In a screen for Drosophila mutations that result in tissue overgrowth, we identified salvador (sav), a gene that promotes both cell cycle exit and cell death. Elevated Cyclin E and DIAP1 levels are found in mutant cells, resulting in delayed cell cycle exit and impaired apoptosis. Salvador contains two WW domains and binds to the Warts (or LATS) protein kinase. The human ortholog of salvador (hWW45) is mutated in three cancer cell lines. Thus, salvador restricts cell numbers in vivo by functioning as a dual regulator of cell proliferation and apoptosis.
Tapon
Nicolas
N
Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown 02129, USA.
Harvey
Kieran F
KF
Bell
Daphne W
DW
Wahrer
Doke C R
DC
Schiripo
Taryn A
TA
Haber
Daniel  A
D
Hariharan
Iswar K
IK
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification*; D002455:Cell Division / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000302:isolation & purification*; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000473:pathology; D005123:Eye / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018816:Genes, cdc / Q000502:physiology*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D011506:Proteins; C415864:SAV1 protein, human; C465504:sav protein, Drosophila; D011494:Protein Kinases; C092745:LATS1 protein, human; C093503:wts protein, Drosophila; D017346:Protein Serine-Threonine Kinases