ArticleMolecular metabolism2017
Systemic insulin sensitivity is regulated by GPS2 inhibition of AKT ubiquitination and activation in adipose tissue.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Regulatory modules of human thermogenic adipocytes: functional genomics of large cohort and Meta-analysis derived marker-genes.BMC genomics · 2021Pooled it
- GPS2 regulates embryonic angiogenesis by enhancing endothelial cell survival through stabilizing HOIP.Cell death and differentiation · 2026Article
- Liquid-liquid phase separation of GPS2-LATS1 promotes colorectal cancer progression by reprogramming lipid metabolism.Oncogene · 2025Article
- Nonproteolytic ubiquitination regulates chromatin occupancy by the NCoR/SMRT/HDAC3 corepressor complex in MCF-7 breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The interplay of factors in metabolic syndrome: understanding its roots and complexity.Molecular medicine (Cambridge, Mass.) · 2024Review
- Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.MedComm · 2024Review
- Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation.Pharmacological research · 2024Article
- GPS2 promotes erythroid differentiation in K562 erythroleukemia cells primarily via NCOR1.International journal of hematology · 2024Article
- GPS2 ameliorates cigarette smoking-induced pulmonary vascular remodeling by modulating the ras-Raf-ERK axis.Respiratory research · 2024Article
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023Review
- DHA-Provoked Reduction in Adipogenesis and Glucose Uptake Could Be Mediated by Gps2 Upregulation in Immature 3T3-L1 Cells.International journal of molecular sciences · 2023Article
- Balanced control of thermogenesis by nuclear receptor corepressors in brown adipose tissue.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Non-proteolytic ubiquitylation in cellular signaling and human disease.Communications biology · 2022Review
- The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism.International journal of molecular sciences · 2022Article
- Akt Is S-Palmitoylated: A New Layer of Regulation for Akt.Frontiers in cell and developmental biology · 2021Article
- Loss of G protein pathway suppressor 2 in human adipocytes triggers lipid remodeling by upregulating ATP binding cassette subfamily G member 1.Molecular metabolism · 2020Article
- Decoding the rosetta stone of mitonuclear communication.Pharmacological research · 2020Review
- Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion.Cell reports · 2020Article
- Knockout of AKAP150 improves impaired BK channel-mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveInsulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT.
methodsThe molecular mechanism of AKT regulation through ubiquitination is first dissected
resultsOur results indicate that K63 ubiquitination is a critical component of AKT activation in the insulin signaling pathway and that counter-regulation of this step is provided by GPS2 preventing AKT ubiquitination through inhibition of Ubc13 enzymatic activity. Removal of this negative checkpoint, through GPS2 downregulation or genetic deletion, results in sustained activation of insulin signaling both
conclusionsOur findings characterize a novel layer of regulation of the insulin signaling pathway based on non-proteolytic ubiquitination of AKT and define GPS2 as a previously unrecognized component of the insulin signaling cascade. In accordance with this role, we have shown that GPS2 presence in adipocytes modulates systemic metabolism by restricting the activation of insulin signaling during the fasted state, whereas in absence of GPS2, the adipose tissue is more efficient at lipid storage, and obesity becomes uncoupled from inflammation and insulin resistance.
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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.