ArticleOncogene2000
The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 255 citations in OpenAlex.
- Evolution of growth factor signaling to the TSC complex to regulate mTORC1.Science signaling · 2025Review
- Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate.Stem cell research & therapy · 2025Review
- Calmodulin enhances mTORC1 signaling by preventing TSC2-Rheb binding.The Journal of biological chemistry · 2025Article
- New insights into tuberous sclerosis complex: from structure to pathogenesis.Frontiers in cell and developmental biology · 2025Review
- Review
- Defining theThyroid : official journal of the American Thyroid Association · 2024Article
- Review
- A Case Report of Malignant Perivascular Epithelioid Cell Tumors of the Uterus and Literature Review.International journal of women's health · 2024Article
- The stress-responsive protein REDD1 and its pathophysiological functions.Experimental & molecular medicine · 2023Review
- Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model.Cell reports. Medicine · 2023Article
- TSC2 regulates tumor susceptibility to TRAIL-mediated T-cell killing by orchestrating mTOR signaling.The EMBO journal · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Malignant perivascular epithelioid cell tumor (PEComa) of the uterus.BMC women's health · 2022Article
- The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization.Biomolecules · 2022Review
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Review
- Regulation of mTOR complexes in long-lived growth hormone receptor knockout and Snell dwarf mice.Aging · 2022Article
- Review
- Brain Symptoms of Tuberous Sclerosis Complex: Pathogenesis and Treatment.International journal of molecular sciences · 2021Review
- Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report here that overexpression of the tuberous sclerosis-1 (TSC1) gene product hamartin results in the inhibition of growth, as well as changes in cell morphology. Growth inhibition was associated with an increase in the endogenous level of the product of the tuberous sclerosis-2 (TSC2) gene, tuberin. As overexpression of tuberin inhibits cell growth, and hamartin is known to bind tuberin, these results suggested that hamartin stabilizes tuberin and this contributes to the inhibition of cell growth. Indeed, transient transfection of TSC1 increased the endogenous level of tuberin, and transient co-transfection of TSC1 with TSC2 resulted in higher tuberin levels. The stabilization was explained by the finding that tuberin is highly ubiquitinated in cells, while the fraction of tuberin that is bound to hamartin is not ubiquitinated. Co-expression of tuberin stabilized hamartin, which is weakly ubiquitinated, in transiently transfected cells. The amino-terminal two-thirds of tuberin was responsible for its ubiquitination and for stabilization of hamartin. A mutant of tuberin from a patient missense mutation of TSC2 was also highly ubiquitinated, and was unable to stabilize hamartin. We conclude that hamartin is a growth inhibitory protein whose biological effect is likely dependent on its interaction with tuberin.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.