ArticleScience signaling2014
REDD1 enhances protein phosphatase 2A-mediated dephosphorylation of Akt to repress mTORC1 signaling.
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 110 papers.
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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.
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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
110 citing papers in PubMed, 149 citations in OpenAlex.
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- Immunomodulatory Effects of Poly-D,L-Lactic Acid on LL-37-Driven Rosacea-like Inflammation via Suppression of mTORC1 Signaling.International journal of molecular sciences · 2026Article
- GSK3β promotes p53/Nrf2-dependent expression of the stress response protein REDD2 in retinal Müller glia exposed to hyperlipidemic conditions.Experimental eye research · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- REDD1/DDIT4 counteracts endoplasmic reticulum stress-induced apoptosis by controlling the expression of death receptor TRAILR2/DR5 in cancer cells.Cell death & disease · 2026Article
- An RNA-sequencing analysis to determine potential upstream transcriptional regulators of essential amino acid deficiency responses in bovine mammary epithelial cells.BMC genomics · 2026Article
- Disease modeling of myocilin mutation-dependent normal tension glaucoma: human retinal ganglion cell susceptibility to unfolded protein response and mTOR signaling.Stem cells (Dayton, Ohio) · 2026Article
- The dual role of autophagy in cartilage degradation: from mechanisms to targeted therapeutics.Frontiers in cell and developmental biology · 2026Review
- Cell Type-Specific mTORC1 Signaling and Translational Control in Synaptic Plasticity and Memory.Journal of neurochemistry · 2025Review
- Glucocorticoid-induced myopathy: a comprehensive review.Journal of neurology · 2025Review
- Rapid proteasomal degradation of the stress response protein REDD2 is mediated by the E3 ligase HUWE1.Biochemical and biophysical research communications · 2025Article
- Resveratrol ameliorates high‑fat diet‑induced insulin resistance via the DDIT4/mTOR pathway in skeletal muscle.Biomedical reports · 2025Article
- Genetic Evidence Supporting a Causal Association Between mTORC1-Dependent Circulating Protein Levels and Diabetic Retinopathy.Translational vision science & technology · 2025Article
- The African swine fever virus B125R protein antagonizes JAK-STAT signalling by promoting the degradation of IFNAR2.Veterinary research · 2025Article
- Lower cytoplasmic expression of DDIT4 is associated with poor prognosis in gastric cancer patients.Discover oncology · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway.Biology direct · 2024Article
- Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
- Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The protein kinase mTOR (mechanistic target of rapamycin) in complex 1 (mTORC1) promotes cell growth and proliferation in response to anabolic stimuli, including growth factors and nutrients. Growth factors activate mTORC1 by stimulating the kinase Akt, which phosphorylates and inhibits the tuberous sclerosis complex [TSC; which is composed of TSC1, TSC2, and TBC1D7 (Tre2-Bub2-Cdc16 domain family member 7)], thereby stimulating the mTORC1 activator Rheb (Ras homolog enriched in brain). We identified the mechanism through which REDD1 (regulated in DNA damage and development 1) represses the mTORC1 signaling pathway. We found that REDD1 promoted the protein phosphatase 2A (PP2A)-dependent dephosphorylation of Akt on Thr(308) but not on Ser(473). Consistent with previous studies showing that phosphorylation of Akt on Thr(308), but not on Ser(473), is necessary for phosphorylation of TSC2, we observed a REDD1-dependent reduction in the phosphorylation of TSC2 and subsequently in the activation state of Rheb. REDD1 and PP2A coimmunoprecipitated with Akt from wild-type but not REDD1 knockout mouse embryonic fibroblasts, suggesting that REDD1 may act as a targeting protein for the catalytic subunit of PP2A. Furthermore, binding to both Akt and PP2A was essential for REDD1 to repress signaling to mTORC1. Overall, the results demonstrate that REDD1 acts not only as a repressor of mTORC1 but also as a constant modulator of the phosphorylation of Akt in response to growth factors and nutrients.
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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.