ArticleEMBO reports2019
Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Dynamic remodeling of the KRAS interactome by direct RAS inhibitors with distinct mechanism of action reveals convergent responses.Oncogene · 2026Article
- Cell-intrinsic insulin signaling defects in human iPS cell-derived hepatocytes in type 2 diabetes.The Journal of clinical investigation · 2025Article
- Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine.Molecular metabolism · 2025Article
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- Shift work promotes adipogenesis via cortisol-dependent downregulation of EGR3-HDAC6 pathway.Cell death discovery · 2024Article
- Article
- Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases.Cell death & disease · 2023Article
- Histone modification in podocyte injury of diabetic nephropathy.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Insulin resistance rewires the metabolic gene program and glucose utilization in human white adipocytes.International journal of obesity (2005) · 2022Article
- S6 kinase 1 at the central node of cell size and ageing.Frontiers in cell and developmental biology · 2022Review
- Protein acetylation: a novel modus of obesity regulation.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Cold-induction of afadin in brown fat supports its thermogenic capacity.Scientific reports · 2021Article
- Insulin-induced serine 22 phosphorylation of retinoid X receptor alpha is dispensable for adipogenesis in brown adipocytes.Adipocyte · 2020Article
- A Cell-Autonomous Signature of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes.Cell metabolism · 2020Article
- HDAC6-mediated α-tubulin deacetylation suppresses autophagy and enhances motility of podocytes in diabetic nephropathy.Journal of cellular and molecular medicine · 2020Article
- Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue.EMBO reports · 2019Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Insulin orchestrates metabolic homeostasis through a complex signaling network for which the precise mechanisms controlling its fine-tuning are not completely understood. Here, we report that Afadin, a scaffold protein, is phosphorylated on S1795 (S1718 in humans) in response to insulin in adipocytes, and this phosphorylation is impaired with obesity and insulin resistance. In turn, loss of Afadin enhances the response to insulin in adipose tissues via upregulation of the insulin receptor protein levels. This happens in a cell-autonomous and phosphorylation-dependent manner. Insulin-stimulated Afadin-S1795 phosphorylation modulates Afadin binding with interaction partners in adipocytes, among which HDAC6 preferentially interacts with phosphorylated Afadin and acts as a key intermediate to suppress insulin receptor protein levels. Adipose tissue-specific Afadin depletion protects against insulin resistance and improves glucose homeostasis in diet-induced obese mice, independently of adiposity. Altogether, we uncover a novel insulin-induced cellular feedback mechanism governed by the interaction of Afadin with HDAC6 to negatively control insulin action in adipocytes, which may offer new strategies to alleviate insulin resistance.
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