ArticleProceedings of the National Academy of Sciences of the United States of America2009
Rheb controls misfolded protein metabolism by inhibiting aggresome formation and autophagy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 101 citations in OpenAlex.
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- Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution.Nature communications · 2024Article
- 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
- Tannic Acid Mitigates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Inflammation, Oxidative Stress, Apoptosis, and Glutamate Toxicity in Rats.International journal of molecular sciences · 2023Article
- HSV-1 cellular model reveals links between aggresome formation and early step of Alzheimer's disease.Translational psychiatry · 2023Review
- Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition.Cell death & disease · 2022Article
- Article
- Aggrephagy Deficiency in the Placenta: A New Pathogenesis of Preeclampsia.International journal of molecular sciences · 2021Review
- Autophagy Paradox of Cancer: Role, Regulation, and Duality.Oxidative medicine and cellular longevity · 2021Review
- AggreCount: an unbiased image analysis tool for identifying and quantifying cellular aggregates in a spatially defined manner.The Journal of biological chemistry · 2020Article
- PP1C and PP2A are p70S6K Phosphatases Whose Inhibition Ameliorates HLD12-Associated Inhibition of Oligodendroglial Cell Morphological Differentiation.Biomedicines · 2020Article
- Upregulation of Neuronal Rheb(S16H) for Hippocampal Protection in the Adult Brain.International journal of molecular sciences · 2020Review
- Nicotinate-curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus.CNS neuroscience & therapeutics · 2019Article
- YdjC chitooligosaccharide deacetylase homolog induces keratin reorganization in lung cancer cells: involvement of interaction between YDJC and CDC16.Oncotarget · 2018Article
- Novel involvement of RhebL1 in sphingosylphosphorylcholine-induced keratin phosphorylation and reorganization: Binding to and activation of AKT1.Oncotarget · 2017Article
- Inhibition of MAPK pathway is essential for suppressing Rheb-Y35N driven tumor growth.Oncogene · 2017Article
- TSC loss distorts DNA replication programme and sensitises cells to genotoxic stress.Oncotarget · 2016Article
- Drugging the addict: non-oncogene addiction as a target for cancer therapy.EMBO reports · 2016Review
- Metformin induces degradation of mTOR protein in breast cancer cells.Cancer medicine · 2016Article
- Exosomes mediate the acquisition of the disease phenotypes by cells with normal genome in tuberous sclerosis complex.Oncogene · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perinuclear aggresome formation is a key mechanism to dispose of misfolded proteins that exceed the degradative capacity of ubiquitin-proteasome and autophagy-lysosome systems. Functional blockade of either degradative system leads to an enhanced aggresome formation. The tuberous sclerosis complex-Ras homologue enriched in brain-mammalian target of rapamycin (TSC-Rheb-mTOR) pathway is known to play a central role in modulating protein synthesis and autophagy. However, in spite of the constitutive activation of mTOR and the abrogated autophagy activity in TSC1- or TSC2-deficient cells, the TSC mutant cells are defective in aggresome formation and undergo apoptosis upon misfolded protein accumulation both in vitro and in vivo. High Rheb activity in TSC mutant cells inhibits aggresome formation and sensitizes cell death in response to misfolded proteins. Surprisingly, this previously unrecognized function of Rheb is independent of TOR complex 1. Active Rheb disrupts the interaction between dynein and misfolded protein cargos, and therefore blocks aggresome formation by inhibiting dynein-dependent transportation of misfolded proteins. This study reveals a function of Rheb in controlling misfolded protein metabolism by modulating aggresome formation.
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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.