Document Detail

TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth.
MedLine Citation:
PMID:  11390358     Owner:  NLM     Status:  MEDLINE    
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.
X Gao; D Pan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Genes & development     Volume:  15     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-06     Completed Date:  2001-07-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1383-92     Citation Subset:  IM    
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9040, USA.
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MeSH Terms
Cell Division
Cell Size
Drosophila Proteins
Flow Cytometry
Genes, Tumor Suppressor*
Insulin / metabolism,  physiology*
Loss of Heterozygosity
Polymerase Chain Reaction
Precipitin Tests
Protein-Serine-Threonine Kinases*
Proteins / genetics*,  metabolism
Proto-Oncogene Proteins / genetics,  metabolism
Proto-Oncogene Proteins c-akt
Receptor, Insulin / genetics
Repressor Proteins / genetics*,  metabolism
Signal Transduction*
Tumor Suppressor Proteins
Grant Support
Reg. No./Substance:
0/Akt1 protein, Drosophila; 0/Drosophila Proteins; 0/Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; 0/Tumor Suppressor Proteins; 0/tuberous sclerosis complex 1 protein; 11061-68-0/Insulin; 169027-60-5/tuberous sclerosis complex 2 protein; EC, Insulin; EC Kinases; EC Proteins c-akt

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