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TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth
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| Zeitschriftentitel: | Genes & Development |
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| Personen und Körperschaften: | , |
| In: | Genes & Development, 15, 2001, 11, S. 1383-1392 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Cold Spring Harbor Laboratory
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>Tuberous sclerosis is a human disease caused by mutations in the<jats:italic>TSC1</jats:italic> or the <jats:italic>TSC2</jats:italic> tumor suppressor gene. Previous studies of a <jats:italic>Drosophila TSC2</jats:italic> homolog suggested a role for the <jats:italic>TSC</jats:italic> genes in maintaining DNA content, with loss of<jats:italic>TSC2</jats:italic> leading to polyploidy and increased cell size. We have isolated mutations in the <jats:italic>Drosophila</jats:italic> homolog of the<jats:italic>TSC1</jats:italic> 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 <jats:italic>TSC1</jats:italic><jats:sup>–</jats:sup> or<jats:italic>TSC2</jats:italic><jats:sup>–</jats:sup> cells are diploid. We find that, strikingly, the heterozygosity of <jats:italic>TSC1</jats:italic> or <jats:italic>TSC2</jats:italic> is sufficient to rescue the lethality of loss-of-function insulin receptor mutants. Further genetic analyses suggest that the <jats:italic>TSC</jats:italic> genes act in a parallel pathway that converges on the insulin pathway downstream from<jats:italic>Akt</jats:italic>. Taken together, our studies identified the <jats:italic>TSC</jats:italic>tumor suppressors as novel negative regulators of insulin signaling.</jats:p> |
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| Umfang: | 1383-1392 |
| ISSN: |
0890-9369
1549-5477 |
| DOI: | 10.1101/gad.901101 |