salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines

Cell. 2002 Aug 23;110(4):467-78. doi: 10.1016/s0092-8674(02)00824-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / genetics*
  • Base Sequence / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / isolation & purification*
  • Cell Division / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / isolation & purification*
  • Eukaryotic Cells / metabolism*
  • Eukaryotic Cells / pathology
  • Eye / embryology
  • Eye / metabolism
  • Eye / ultrastructure
  • Eye Abnormalities / genetics
  • Eye Abnormalities / metabolism
  • Eye Abnormalities / pathology
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, cdc / physiology*
  • Genetic Testing
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation / genetics
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phenotype
  • Photoreceptor Cells, Invertebrate / abnormalities
  • Photoreceptor Cells, Invertebrate / metabolism
  • Photoreceptor Cells, Invertebrate / pathology
  • Protein Kinases*
  • Protein Structure, Tertiary / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Tumor Cells, Cultured

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Proteins
  • SAV1 protein, human
  • sav protein, Drosophila
  • Protein Kinases
  • LATS1 protein, human
  • wts protein, Drosophila
  • Protein-Serine-Threonine Kinases