ArticleThe Journal of clinical investigation2010
The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous sclerosis complex and Drosophila external sensory organ development.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC).Oncogene · 2026Article
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model.Cell reports. Medicine · 2023Article
- Upregulation of acid ceramidase contributes to tumor progression in tuberous sclerosis complex.JCI insight · 2023Article
- "A fly appeared": sable, a classic Drosophila mutation, maps to Yippee, a gene affecting body color, wings, and bristles.G3 (Bethesda, Md.) · 2022Article
- Blocking the Farnesyl Pocket of PDEδ Reduces Rheb-Dependent mTORC1 Activation and Survival ofFrontiers in pharmacology · 2022Article
- Tsc1 regulates tight junction independent of mTORC1.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Inhibition of the mechanistic target of rapamycin induces cell survival via MAPK in tuberous sclerosis complex.Orphanet journal of rare diseases · 2020Article
- Rapamycin and dexamethasone during pregnancy prevent tuberous sclerosis complex-associated cystic kidney disease.JCI insight · 2020Article
- Notch pathway: a bistable inducer of biological noise?Cell communication and signaling : CCS · 2019Review
- Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway.Journal of molecular cell biology · 2019Article
- The Codon 72Molecular cancer research : MCR · 2019Article
- Lens differentiation is controlled by the balance between PDGF and FGF signaling.PLoS biology · 2019Article
- Rheb1 loss leads to increased hematopoietic stem cell proliferation and myeloid-biased differentiationHaematologica · 2019Article
- A distinct microRNA expression profile is associated with α[Neurobiology of disease · 2018Article
- Notch transactivates Rheb to maintain the multipotency of TSC-null cells.Nature communications · 2017Article
- Rheb Inhibits Beiging of White Adipose Tissue via PDE4D5-Dependent Downregulation of the cAMP-PKA Signaling Pathway.Diabetes · 2017Article
- Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.Cancer science · 2017Review
- Exosomes mediate the acquisition of the disease phenotypes by cells with normal genome in tuberous sclerosis complex.Oncogene · 2016Article
- mTORC1 Prevents Preosteoblast Differentiation through the Notch Signaling Pathway.PLoS genetics · 2015Article
Corrections and comments
- Commented on by
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in either of the genes encoding the tuberous sclerosis complex (TSC), TSC1 and TSC2, result in a multisystem tumor disorder characterized by lesions with unusual lineage expression patterns. How these unusual cell-fate determination patterns are generated is unclear. We therefore investigated the role of the TSC in the Drosophila external sensory organ (ESO), a classic model of asymmetric cell division. In normal development, the sensory organ precursor cell divides asymmetrically through differential regulation of Notch signaling to produce a pIIa and a pIIb cell. We report here that inactivation of Tsc1 and overexpression of the Ras homolog Rheb each resulted in duplication of the bristle and socket cells, progeny of the pIIa cell, and loss of the neuronal cell, a product of pIIb cell division. Live imaging of ESO development revealed this cell-fate switch occurred at the pIIa-pIIb 2-cell stage. In human angiomyolipomas, benign renal neoplasms often found in tuberous sclerosis patients, we found evidence of Notch receptor cleavage and Notch target gene activation. Further, an angiomyolipoma-derived cell line carrying biallelic TSC2 mutations exhibited TSC2- and Rheb-dependent Notch activation. Finally, inhibition of Notch signaling using a gamma-secretase inhibitor suppressed proliferation of Tsc2-null rat cells in a xenograft model. Together, these data indicate that the TSC and Rheb regulate Notch-dependent cell-fate decision in Drosophila and Notch activity in mammalian cells and that Notch dysregulation may underlie some of the distinctive clinical and pathologic features of TSC.
Indexed as
Identifiers
What OpenQuestion holds
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.