ArticleThe Journal of biological chemistry2012
Endoproteolytic cleavage of TUG protein regulates GLUT4 glucose transporter translocation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Altered Molecular Regulation of TUG Is a Central Feature of Insulin-Resistant Human Adipose Tissue.Diabetes · 2026Article
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- TUG protein acts through a disordered region to organize the early secretory pathway.Nature communications · 2025Article
- UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling.Nature immunology · 2024Article
- UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling.Research square · 2024Article
- Functional Classification of Fusion Proteins in Sarcoma.Cancers · 2024Review
- GA signaling expands: The plant UBX domain-containing protein 1 is a binding partner for the GA receptor.Plant physiology · 2022Article
- Inhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes.Scientific reports · 2022Article
- Review
- Article
- GLUT4 On the move.The Biochemical journal · 2022Article
- Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle.Frontiers in endocrinology · 2022Review
- The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes.The EMBO journal · 2021Article
- Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake.Nature metabolism · 2021Article
- The yeast protein Ubx4p contributes to mitochondrial respiration and lithium-galactose-mediated activation of the unfolded protein response.The Journal of biological chemistry · 2020Article
- GluT4: A central player in hippocampal memory and brain insulin resistance.Experimental neurology · 2020Review
- GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.The Yale journal of biology and medicine · 2019Review
- A high-throughput chemical-genetics screen in murine adipocytes identifies insulin-regulatory pathways.The Journal of biological chemistry · 2019Article
- Mechanisms of Insulin Action and Insulin Resistance.Physiological reviews · 2018Review
- Usp25m protease regulates ubiquitin-like processing of TUG proteins to control GLUT4 glucose transporter translocation in adipocytes.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
To promote glucose uptake into fat and muscle cells, insulin causes the translocation of GLUT4 glucose transporters from intracellular vesicles to the cell surface. Previous data support a model in which TUG traps GLUT4-containing vesicles and tethers them intracellularly in unstimulated cells and in which insulin mobilizes this pool of vesicles by releasing this tether. Here we show that TUG undergoes site-specific endoproteolytic cleavage, which separates a GLUT4-binding, N-terminal region of TUG from a C-terminal region previously suggested to bind an intracellular anchor. Cleavage is accelerated by insulin stimulation in 3T3-L1 adipocytes and is highly dependent upon adipocyte differentiation. The N-terminal TUG cleavage product has properties of a novel 18-kDa ubiquitin-like modifier, which we call TUGUL. The C-terminal product is observed at the expected size of 42 kDa and also as a 54-kDa form that is released from membranes into the cytosol. In transfected cells, intact TUG links GLUT4 to PIST and also binds Golgin-160 through its C-terminal region. PIST is an effector of TC10α, a GTPase previously shown to transmit an insulin signal required for GLUT4 translocation, and we show using RNAi that TC10α is required for TUG proteolytic processing. Finally, we demonstrate that a cleavage-resistant form of TUG does not support highly insulin-responsive GLUT4 translocation or glucose uptake in 3T3-L1 adipocytes. Together with previous results, these data support a model whereby insulin stimulates TUG cleavage to liberate GLUT4 storage vesicles from the Golgi matrix, which promotes GLUT4 translocation to the cell surface and enhances glucose uptake.
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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.