TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth

X. Gao, D. Pan

Research output: Contribution to journalArticle

360 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1383-1392
Number of pages10
JournalGenes and Development
Volume15
Issue number11
DOIs
StatePublished - Jun 21 2001

Fingerprint

Insulin
Drosophila
Growth
Genes
Neoplasms
Mutation
Tuberous Sclerosis
Polyploidy
Insulin Receptor
Tumor Suppressor Genes
Diploidy
Cell Size
DNA

Keywords

  • Akt
  • Cell size
  • Insulin signaling
  • Tumor suppressor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. / Gao, X.; Pan, D.

In: Genes and Development, Vol. 15, No. 11, 21.06.2001, p. 1383-1392.

Research output: Contribution to journalArticle

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