ArticleSmall GTPases2011
Consequences of interrupted Rheb-to-AMPK feedback signaling in tuberous sclerosis complex and cancer.
Article in Small GTPases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 18 citations in OpenAlex.
- Delineating the Transcriptional and Phenotypic Impact from Biotherapeutic Glycoengineering.bioRxiv : the preprint server for biology · 2026Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Targeting the mTOR-Autophagy Axis: Unveiling Therapeutic Potentials in Osteoporosis.Biomolecules · 2024Review
- Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy.Cell communication and signaling : CCS · 2024Review
- Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome.Cell stress · 2024Article
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- The Role of Autophagy and Mitophagy in Bone Metabolic Disorders.International journal of biological sciences · 2020Review
- Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling.Journal of cell science · 2019Article
- Tau and mTOR: The Hotspots for Multifarious Diseases in Alzheimer's Development.Frontiers in neuroscience · 2018Review
- A possible role for AMP-activated protein kinase activated by metformin and AICAR in human granulosa cells.Reproductive biology and endocrinology : RB&E · 2015Article
- Management of lymphangioleiomyomatosis.F1000prime reports · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rheb is a small GTPase primarily known for activating mammalian target of rapamycin complex 1 (mTORC1) and promoting cell growth in response to insulin and nutrients (amino acids, glucose). Shortage of glucose activates adenosine 5'-monophosphate-activated protein kinase (AMPK), which induces catabolic processes that produce ATP and suppresses energy-consuming anabolic reactions. As part of the latter response, AMPK activates the TSC1-TSC2 tumor suppressor complex, which in turn inhibits Rheb, thereby reducing mTORC1 activity and consequently suppressing protein synthesis. We recently identified an mTORC1-independent Rheb-to-AMPK feedback signaling loop in Tsc2-null in vitro models of Tuberous Sclerosis Complex (TSC). In addition to activating AMPK, Rheb reduced the nuclear levels of the cyclin-dependent kinase inhibitor p27(KIP1) (p27). Importantly, Rheb-mediated repression of p27 correlated with activation of Cdk2 and cell proliferation, and with tumor formation by TSC cells. Considering that AMPK was previously reported to regulate stability and subcellular localization of p27, we hypothesize that Rheb regulates p27 in TSC cells by activating AMPK. This article discusses how Rheb-to-AMPK, and p27 signaling may impact on disease progression and treatment of TSC, including sporadic lymphangioleiomyomatosis (S-LAM) and malignancies.
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.