Non-canonical functions of a mutant TSC2 protein in mitotic division.
Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. TSC is caused by mutations in the TSC1 or TSC2 genes, which encode the hamartin/tuberin proteins respectively. These proteins function as a heterodimer that negatively reg...
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Public Library of Science (PLoS)
2023-01-01
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Series: | PLoS ONE |
Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292086&type=printable |
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author | Mary-Bronwen L Chalkley Rachel B Mersfelder Maria Sundberg Laura C Armstrong Mustafa Sahin Rebecca A Ihrie Kevin C Ess |
author_facet | Mary-Bronwen L Chalkley Rachel B Mersfelder Maria Sundberg Laura C Armstrong Mustafa Sahin Rebecca A Ihrie Kevin C Ess |
author_sort | Mary-Bronwen L Chalkley |
collection | DOAJ |
description | Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. TSC is caused by mutations in the TSC1 or TSC2 genes, which encode the hamartin/tuberin proteins respectively. These proteins function as a heterodimer that negatively regulates the mechanistic Target of Rapamycin Complex 1 (mTORC1). TSC research has focused on the effects of mTORC1, a critical signaling hub, on regulation of diverse cell processes including metabolism, cell growth, translation, and neurogenesis. However, non-canonical functions of TSC2 are not well studied, and the potential disease-relevant biological mechanisms of mutations affecting these functions are not well understood. We observed aberrant multipolar mitotic division, a novel phenotype, in TSC2 mutant iPSCs. The multipolar phenotype is not meaningfully affected by treatment with the inhibitor rapamycin. We further observed dominant negative activity of the mutant form of TSC2 in producing the multipolar division phenotype. These data expand the knowledge of TSC2 function and pathophysiology which will be highly relevant to future treatments for patients with TSC. |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-24T23:18:53Z |
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spelling | doaj.art-d45f6b6c25b340218f4d2f8d48a9b3ea2024-03-17T05:30:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011810e029208610.1371/journal.pone.0292086Non-canonical functions of a mutant TSC2 protein in mitotic division.Mary-Bronwen L ChalkleyRachel B MersfelderMaria SundbergLaura C ArmstrongMustafa SahinRebecca A IhrieKevin C EssTuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. TSC is caused by mutations in the TSC1 or TSC2 genes, which encode the hamartin/tuberin proteins respectively. These proteins function as a heterodimer that negatively regulates the mechanistic Target of Rapamycin Complex 1 (mTORC1). TSC research has focused on the effects of mTORC1, a critical signaling hub, on regulation of diverse cell processes including metabolism, cell growth, translation, and neurogenesis. However, non-canonical functions of TSC2 are not well studied, and the potential disease-relevant biological mechanisms of mutations affecting these functions are not well understood. We observed aberrant multipolar mitotic division, a novel phenotype, in TSC2 mutant iPSCs. The multipolar phenotype is not meaningfully affected by treatment with the inhibitor rapamycin. We further observed dominant negative activity of the mutant form of TSC2 in producing the multipolar division phenotype. These data expand the knowledge of TSC2 function and pathophysiology which will be highly relevant to future treatments for patients with TSC.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292086&type=printable |
spellingShingle | Mary-Bronwen L Chalkley Rachel B Mersfelder Maria Sundberg Laura C Armstrong Mustafa Sahin Rebecca A Ihrie Kevin C Ess Non-canonical functions of a mutant TSC2 protein in mitotic division. PLoS ONE |
title | Non-canonical functions of a mutant TSC2 protein in mitotic division. |
title_full | Non-canonical functions of a mutant TSC2 protein in mitotic division. |
title_fullStr | Non-canonical functions of a mutant TSC2 protein in mitotic division. |
title_full_unstemmed | Non-canonical functions of a mutant TSC2 protein in mitotic division. |
title_short | Non-canonical functions of a mutant TSC2 protein in mitotic division. |
title_sort | non canonical functions of a mutant tsc2 protein in mitotic division |
url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292086&type=printable |
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