ArticlePloS one2020
Investigating AKT activation and autophagy in immunoproteasome-deficient retinal cells.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
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- The pro-differentiating capability of a flavonoid-rich extract of Citrus bergamia juice prompts autophagic death in THP-1 cells.Scientific reports · 2024Article
- LVING reveals the intracellular structure of cell growth.Scientific reports · 2024Article
- Review
- Duality of Valproic Acid Effects on Inflammation, Oxidative Stress and Autophagy in Human Eosinophilic Cells.International journal of molecular sciences · 2023Article
- Role of TFEB in Diseases Associated with Lysosomal Dysfunction.Advances in experimental medicine and biology · 2023Article
- Article
- Inhibition of p21 activates Akt kinase to trigger ROS-induced autophagy and impacts on tumor growth rate.Cell death & disease · 2022Article
- Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.Genes & diseases · 2022Review
- Human iPSC- and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2022Article
- Regulation of Autophagy by the Glycogen Synthase Kinase-3 (GSK-3) Signaling Pathway.International journal of molecular sciences · 2022Review
- Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Effects ofInternational journal of ophthalmology · 2022Article
- Proteostasis Dysfunction in Aged Mammalian Cells. The Stressful Role of Inflammation.Frontiers in molecular biosciences · 2021Review
- A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Two major proteolytic systems, the proteasome and the autophagy pathway, are key components of the proteostasis network. The immunoproteasome, a proteasome subtype, and autophagy are upregulated under stress conditions, forming a coordinated unit designed to minimize the effect of cell stress. We investigated how genetic ablation of the LMP2 immunoproteasome subunit affects autophagy in retinal pigment epithelium (RPE) from WT and LMP2 knockout mice. We monitored autophagy regulation by measuring LC3, phosphorylation of AKT (S473), and phosphorylation of S6, a downstream readout of AKT (mTOR) pathway activation. We also evaluated transcription factor EB (TFEB) nuclear translocation, a transcription factor that controls expression of autophagy and lysosome genes. WT and LMP2 KO cells were monitored after treatment with EBSS to stimulate autophagy, insulin to stimulate AKT, or an AKT inhibitor (trehalose or MK-2206). Under basal conditions, we observed hyper-phosphorylation of AKT and S6, as well as lower nuclear-TFEB content in LMP2 KO RPE compared with WT. AKT inhibitors MK-2206 and trehalose significantly inhibited AKT phosphorylation and stimulated nuclear translocation of TFEB. Starvation and AKT inhibition upregulated autophagy, albeit to a lesser extent in LMP2 KO RPE. These data support the idea that AKT hyper-activation is an underlying cause of defective autophagy regulation in LMP2 KO RPE, revealing a unique link between two proteolytic systems and a previously unknown function in autophagy regulation by the immunoproteasome.
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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.