Article ; Online: Non-canonical functions of a mutant TSC2 protein in mitotic division.
2023 Volume 18, Issue 10, Page(s) e0292086
Abstract: 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 ...
| Abstract | 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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| MeSH term(s) | Humans ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mutant Proteins ; Signal Transduction ; Tuberous Sclerosis Complex 2 Protein/genetics ; Tuberous Sclerosis Complex 2 Protein/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism |
| Chemical Substances | Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mutant Proteins ; Tuberous Sclerosis Complex 2 Protein ; Tumor Suppressor Proteins ; TSC2 protein, human |
| Language | English |
| Publishing date | 2023-10-04 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2267670-3 |
| ISSN | 1932-6203 ; 1932-6203 |
| ISSN (online) | 1932-6203 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0292086 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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