ArticleThe Journal of clinical investigation2017
Tuberous sclerosis complex inactivation disrupts melanogenesis via mTORC1 activation.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- mTOR inhibition reprograms cellular lipid homeostasis by inducing alternative lipid uptake and promoting cholesterol transport.Molecular cell · 2025Article
- TSC complex decrease the expression of mTOR by regulated miR-199b-3p.Scientific reports · 2025Article
- mTORC1 activity negatively regulates human hair follicle growth and pigmentation.EMBO reports · 2023Article
- TSC2 regulates tumor susceptibility to TRAIL-mediated T-cell killing by orchestrating mTOR signaling.The EMBO journal · 2023Article
- Diagnosis of Mosaic Tuberous Sclerosis Complex Using Next-Generation Sequencing of Subtle or Unusual Cutaneous Findings.JID innovations : skin science from molecules to population health · 2023Article
- A Comprehensive Review of Mammalian Pigmentation: Paving the Way for Innovative Hair Colour-Changing Cosmetics.Biology · 2023Review
- Review
- Case report: tuberous sclerosis and persistent hyperplastic primary vitreous.BMC ophthalmology · 2022Article
- Histopathological features of fibrous cephalic plaques in tuberous sclerosis complex.Histopathology · 2021Article
- Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Inhibition of the Wnt/β-catenin signaling pathway reduces autophagy levels in complement treated podocytes.Experimental and therapeutic medicine · 2021Article
- Limited survival and impaired hepatic fasting metabolism in mice with constitutive Rag GTPase signaling.Nature communications · 2021Article
- Skin Pigmentation Abnormalities and Their Possible Relationship with Skin Aging.International journal of molecular sciences · 2021Review
- CrossTORC and WNTegration in Disease: Focus on Lymphangioleiomyomatosis.International journal of molecular sciences · 2021Review
- Roles of Src family kinase, Ras, and mTOR signaling in intestinal epithelial homeostasis and tumorigenesis.Cancer science · 2021Review
- Regulation of colonic epithelial cell homeostasis by mTORC1.Scientific reports · 2020Article
- Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes.Molecular biology of the cell · 2020Article
- Chronic mTOR activation induces a degradative smooth muscle cell phenotype.The Journal of clinical investigation · 2020Article
- Combination therapy with ropivacaine-loaded liposomes and nutrient deprivation for simultaneous cancer therapy and cancer pain relief.Theranostics · 2020Article
- Serum Proteomic Profiling Analysis of Rats Chronically Exposed to Arsenic.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant tumor-suppressor gene syndrome caused by inactivating mutations in either TSC1 or TSC2, and the TSC protein complex is an essential regulator of mTOR complex 1 (mTORC1). Patients with TSC develop hypomelanotic macules (white spots), but the molecular mechanisms underlying their formation are not fully characterized. Using human primary melanocytes and a highly pigmented melanoma cell line, we demonstrate that reduced expression of either TSC1 or TSC2 causes reduced pigmentation through mTORC1 activation, which results in hyperactivation of glycogen synthase kinase 3β (GSK3β), followed by phosphorylation of and loss of β-catenin from the nucleus, thereby reducing expression of microphthalmia-associated transcription factor (MITF), and subsequent reductions in tyrosinase and other genes required for melanogenesis. Genetic suppression or pharmacological inhibition of this signaling cascade at multiple levels restored pigmentation. Importantly, primary melanocytes isolated from hypomelanotic macules from 6 patients with TSC all exhibited reduced TSC2 protein expression, and 1 culture showed biallelic mutation in TSC2, one of which was germline and the second acquired in the melanocytes of the hypomelanotic macule. These findings indicate that the TSC/mTORC1/AKT/GSK3β/β-catenin/MITF axis plays a central role in regulating melanogenesis. Interventions that enhance or diminish mTORC1 activity or other nodes in this pathway in melanocytes could potentially modulate pigment production.
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Registered trials
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.