ArticlePLoS genetics2014
Ribosomal protein mutations induce autophagy through S6 kinase inhibition of the insulin pathway.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 78 citations in OpenAlex.
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- Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma.Molecular cancer · 2024Article
- Research Progress of Ribosomal Proteins in Reproductive Development.International journal of molecular sciences · 2024Review
- Mechanisms of spinophilin-dependent pancreas dysregulation in obesity.American journal of physiology. Endocrinology and metabolism · 2024Article
- Disruption of mitochondrial energy metabolism is a putative pathogenesis of Diamond-Blackfan anemia.iScience · 2024Article
- The Molecular and Genetic Mechanisms of Inherited Bone Marrow Failure Syndromes: The Role of Inflammatory Cytokines in Their Pathogenesis.Biomolecules · 2023Review
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- Evaluation of the mTORC activity in the presence of Toxoplasma gondii and azathioprine in human monocyte cell line.BMC microbiology · 2023Article
- Mechanisms of spinophilin-dependent pancreas dysregulation underlying diabesity.bioRxiv : the preprint server for biology · 2023Article
- Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment.Frontiers in oncology · 2023Article
- Involvement of Target of Rapamycin (TOR) Signaling in the Regulation of Crosstalk between Ribosomal Protein Small Subunit 6 Kinase-1 (RPS6K-1) and Ribosomal Proteins.Plants (Basel, Switzerland) · 2023Article
- Diabetes risk loci-associated pathways are shared across metabolic tissues.BMC genomics · 2022Article
- Article
- Effect of Glucocorticosteroids in Diamond-Blackfan Anaemia: Maybe Not as Elusive as It Seems.International journal of molecular sciences · 2022Review
- The Role of iPSC Modeling Toward Projection of Autophagy Pathway in Disease Pathogenesis: Leader or Follower.Stem cell reviews and reports · 2021Review
- Oxidative DNA Damage, Inflammatory Signature, and Altered Erythrocytes Properties in Diamond-Blackfan Anemia.International journal of molecular sciences · 2020Article
- Emerging mechanisms of cell competition.Nature reviews. Genetics · 2020Review
- Ribosomopathies: New Therapeutic Perspectives.Cells · 2020Review
- Diamond-Blackfan anemia.Blood · 2020Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Mutations affecting the ribosome lead to several diseases known as ribosomopathies, with phenotypes that include growth defects, cytopenia, and bone marrow failure. Diamond-Blackfan anemia (DBA), for example, is a pure red cell aplasia linked to the mutation of ribosomal protein (RP) genes. Here we show the knock-down of the DBA-linked RPS19 gene induces the cellular self-digestion process of autophagy, a pathway critical for proper hematopoiesis. We also observe an increase of autophagy in cells derived from DBA patients, in CD34+ erythrocyte progenitor cells with RPS19 knock down, in the red blood cells of zebrafish embryos with RP-deficiency, and in cells from patients with Shwachman-Diamond syndrome (SDS). The loss of RPs in all these models results in a marked increase in S6 kinase phosphorylation that we find is triggered by an increase in reactive oxygen species (ROS). We show that this increase in S6 kinase phosphorylation inhibits the insulin pathway and AKT phosphorylation activity through a mechanism reminiscent of insulin resistance. While stimulating RP-deficient cells with insulin reduces autophagy, antioxidant treatment reduces S6 kinase phosphorylation, autophagy, and stabilization of the p53 tumor suppressor. Our data suggest that RP loss promotes the aberrant activation of both S6 kinase and p53 by increasing intracellular ROS levels. The deregulation of these signaling pathways is likely playing a major role in the pathophysiology of ribosomopathies.
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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.