ArticleScience signaling2014
The adaptor protein p66Shc inhibits mTOR-dependent anabolic metabolism.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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
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Who cites it
23 citing papers in PubMed, 1 citations in OpenAlex.
- The Role of p66Shc in Cancer: Molecular Mechanisms and Therapeutic Implications.Journal of cellular and molecular medicine · 2025Review
- p66Shc Protein-Oxidative Stress Sensor or Redox Enzyme: Its Potential Role in Mitochondrial Metabolism of Human Breast Cancer.Cancers · 2024Article
- The Role of the Redox Enzyme p66Shc in Biological Aging of the Lung.Aging and disease · 2024Article
- p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress.Redox biology · 2024Article
- Exploring the Gut-Mitochondrial Axis: p66Shc Adapter Protein and Its Implications for Metabolic Disorders.International journal of molecular sciences · 2024Review
- The p66International journal of molecular sciences · 2023Review
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- p66ShcA potentiates the cytotoxic response of triple-negative breast cancers to PARP inhibitors.JCI insight · 2021Article
- Beneficial Effects of Melatonin in the Ovarian Transport Medium on In Vitro Embryo Production of Iberian Red Deer (Animals : an open access journal from MDPI · 2020Article
- P66Shc: A Pleiotropic Regulator of B Cell Trafficking and a Gatekeeper in Chronic Lymphocytic Leukemia.Cancers · 2020Review
- p66ShcA functions as a contextual promoter of breast cancer metastasis.Breast cancer research : BCR · 2020Article
- Regulation of Selective B Cell Autophagy by the Pro-oxidant Adaptor p66SHC.Frontiers in cell and developmental biology · 2020Review
- Modulation of Obesity and Insulin Resistance by the Redox Enzyme and Adaptor Protein p66International journal of molecular sciences · 2019Review
- p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity.Scientific reports · 2018Review
- Reactive Oxygen Species in Metabolic and Inflammatory Signaling.Circulation research · 2018Review
- The pro-oxidant adaptor p66SHC promotes B cell mitophagy by disrupting mitochondrial integrity and recruiting LC3-II.Autophagy · 2018Article
- New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases.British journal of pharmacology · 2017Review
- mTOR complex 1 signalling regulates the balance between lipid synthesis and oxidation in hypoxia lymphocytes.Bioscience reports · 2017Article
- P66Shc, a key regulator of metabolism and mitochondrial ROS production, is dysregulated by mouse embryo culture.Molecular human reproduction · 2016Article
- p66Shc: A novel biomarker of tubular oxidative injury in patients with diabetic nephropathy.Scientific reports · 2016Article
Corrections and comments
- Erratum issuedLamming, Dudley A [corrected to Lamming, Dudley W]
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Adaptor proteins link surface receptors to intracellular signaling pathways and potentially control the way cells respond to nutrient availability. Mice deficient in p66Shc, the most recently evolved isoform of the Shc1 adaptor proteins and a mediator of receptor tyrosine kinase signaling, display resistance to diabetes and obesity. Using quantitative mass spectrometry, we found that p66Shc inhibited glucose metabolism. Depletion of p66Shc enhanced glycolysis and increased the allocation of glucose-derived carbon into anabolic metabolism, characteristics of a metabolic shift called the Warburg effect. This change in metabolism was mediated by the mammalian target of rapamycin (mTOR) because inhibition of mTOR with rapamycin reversed the glycolytic phenotype caused by p66Shc deficiency. Thus, unlike the other isoforms of Shc1, p66Shc appears to antagonize insulin and mTOR signaling, which limits glucose uptake and metabolism. Our results identify a critical inhibitory role for p66Shc in anabolic metabolism.
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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.