ArticleCell2017
The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover.
Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed.
- E3 ligase FBXO2-mediated protein stability of insulin receptor regulates adipogenesis and metabolic health in obesity.Cell death & disease · 2026Article
- Partitioning of the truncated insulin receptor DAF-2B between homodimers and heterodimers influences insulin signaling in C. elegans.PLoS genetics · 2026Article
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- STUB1-induced polyubiquitination of SIK3 in alveolar type 2 epithelial cells alleviates severity and outcomes of acute lung injury.Cell death & disease · 2026Article
- A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer's and Parkinson's Disease.Journal of molecular neuroscience : MN · 2026Review
- Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?The Journal of biological chemistry · 2026Review
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- Early life starvation and Hedgehog-related signaling activate innate immunity downstream of daf-18/PTEN and lin-35/Rb causing developmental pathology in adult C. elegans.PLoS genetics · 2025Article
- Review
- Stub1 Acetylation by CBP/p300 Attenuates Chronic Hypoxic-Driven Pulmonary Hypertension by Suppressing HIF-2α.American journal of respiratory cell and molecular biology · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- CHIP and aging: a key regulator of proteostasis and cellular senescence.Biogerontology · 2025Review
- Developmental and conditional regulation of DAF-2/INSR ubiquitination in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2025Article
- Chaperone Proteins: The Rising Players in Muscle Atrophy.Journal of cachexia, sarcopenia and muscle · 2025Review
- Decreased Hsp90 activity protects against TDP-43 neurotoxicity in a C. elegans model of amyotrophic lateral sclerosis.PLoS genetics · 2024Article
- CHIP ameliorates nonalcoholic fatty liver disease via promoting K63- and K27-linked STX17 ubiquitination to facilitate autophagosome-lysosome fusion.Nature communications · 2024Article
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Improved resilience and proteostasis mediate longevity upon DAF-2 degradation in old age.GeroScience · 2024Article
- Short-Term Statin Therapy Induces Hepatic Insulin Resistance Through HNF4α/PAQR9/PPM1α Axis Regulated AKT Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans.Aging cell · 2024Article
23 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Aging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging. INSR is a direct target of CHIP, which triggers receptor monoubiquitylation and endocytic-lysosomal turnover to promote longevity. However, upon proteotoxic stress conditions and during aging, CHIP is recruited toward disposal of misfolded proteins, reducing its capacity to degrade the INSR. Our study indicates a competitive relationship between proteostasis and longevity regulation through CHIP-assisted proteolysis, providing a mechanistic concept for understanding the impact of proteome imbalance on aging.
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