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TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth
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| Zeitschriftentitel: | Genes & Development |
|---|---|
| Personen und Körperschaften: | , |
| In: | Genes & Development, 15, 2001, 11, S. 1383-1392 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Cold Spring Harbor Laboratory
|
| Schlagwörter: |
| author_facet |
Gao, Xinsheng Pan, Duojia Gao, Xinsheng Pan, Duojia |
|---|---|
| author |
Gao, Xinsheng Pan, Duojia |
| spellingShingle |
Gao, Xinsheng Pan, Duojia Genes & Development TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth Developmental Biology Genetics |
| author_sort |
gao, xinsheng |
| spelling |
Gao, Xinsheng Pan, Duojia 0890-9369 1549-5477 Cold Spring Harbor Laboratory Developmental Biology Genetics http://dx.doi.org/10.1101/gad.901101 <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> <i>TSC1</i> and <i>TSC2</i> tumor suppressors antagonize insulin signaling in cell growth Genes & Development |
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10.1101/gad.901101 |
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Biologie |
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Cold Spring Harbor Laboratory, 2001 |
| imprint_str_mv |
Cold Spring Harbor Laboratory, 2001 |
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0890-9369 1549-5477 |
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2001 |
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Genes & Development |
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| title |
TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_unstemmed |
TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_full |
TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_fullStr |
TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_full_unstemmed |
TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_short |
TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_sort |
<i>tsc1</i> and <i>tsc2</i> tumor suppressors antagonize insulin signaling in cell growth |
| topic |
Developmental Biology Genetics |
| url |
http://dx.doi.org/10.1101/gad.901101 |
| publishDate |
2001 |
| physical |
1383-1392 |
| description |
<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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| author | Gao, Xinsheng, Pan, Duojia |
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| author_sort | gao, xinsheng |
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| description | <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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| imprint | Cold Spring Harbor Laboratory, 2001 |
| imprint_str_mv | Cold Spring Harbor Laboratory, 2001 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| series | Genes & Development |
| source_id | 49 |
| spelling | Gao, Xinsheng Pan, Duojia 0890-9369 1549-5477 Cold Spring Harbor Laboratory Developmental Biology Genetics http://dx.doi.org/10.1101/gad.901101 <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> <i>TSC1</i> and <i>TSC2</i> tumor suppressors antagonize insulin signaling in cell growth Genes & Development |
| spellingShingle | Gao, Xinsheng, Pan, Duojia, Genes & Development, TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth, Developmental Biology, Genetics |
| title | TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_full | TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_fullStr | TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_full_unstemmed | TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_short | TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| title_sort | <i>tsc1</i> and <i>tsc2</i> tumor suppressors antagonize insulin signaling in cell growth |
| title_unstemmed | TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth |
| topic | Developmental Biology, Genetics |
| url | http://dx.doi.org/10.1101/gad.901101 |