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TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth.

Tuberous sclerosis is a human disease caused by mutations in the TSC1 or the TSC2 tumor suppressor gene. Previous studies of a Drosophila TSC2 homolog suggested a role for the TSC genes in maintaining DNA content, with loss of TSC2 leading to polyploidy and increased cell size. We have isolated mutations in the Drosophila homolog of the TSC1 gene. We show that TSC1 and TSC2 form a complex and function in a common pathway to control cellular growth. Unlike previous studies, our work shows that TSC1(-) or TSC2(-) cells are diploid. We find that, strikingly, the heterozygosity of TSC1 or TSC2 is sufficient to rescue the lethality of loss-of-function insulin receptor mutants. Further genetic analyses suggest that the TSC genes act in a parallel pathway that converges on the insulin pathway downstream from Akt. Taken together, our studies identified the TSC tumor suppressors as novel negative regulators of insulin signaling.

Pubmed ID: 11390358

Authors

  • Gao X
  • Pan D

Journal

Genes & development

Publication Data

June 1, 2001

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM62323

Mesh Terms

  • Animals
  • Cell Division
  • Cell Size
  • Diploidy
  • Drosophila
  • Drosophila Proteins
  • Flow Cytometry
  • Genes, Tumor Suppressor
  • Insulin
  • Loss of Heterozygosity
  • Mutation
  • Polymerase Chain Reaction
  • Precipitin Tests
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Receptor, Insulin
  • Repressor Proteins
  • Signal Transduction
  • Tumor Suppressor Proteins