ArticleNature communications2023
p21-activated kinase 4 suppresses fatty acid β-oxidation and ketogenesis by phosphorylating NCoR1.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 19 citations in OpenAlex.
- p21-activated kinase 4 drives hepatic stellate cell activation and liver fibrosis through the phosphorylation of YAP at T428.Signal transduction and targeted therapy · 2026Article
- IL-10 attenuates metabolic dysfunction-associated steatotic liver disease via modulation of hepatic responses to lipotoxicity.JCI insight · 2026Article
- Single-nucleus interrogation of primate small intestinal aging reveals NCoR1 decline as a conserved feature that is reversed by metformin.Nature aging · 2026Article
- Polystyrene nanoplastics induce hepatic steatosis by disrupting autophagic degradation of NCoR1 and suppressing PPARα-mediated fatty acid oxidation.Journal of nanobiotechnology · 2026Article
- Article
- PAK4 in metabolic diseases: regulation by nutrient signals and therapeutic implications.Experimental & molecular medicine · 2026Review
- Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling.Nature communications · 2026Article
- Lipid metabolism-MAFLD crosstalk: mechanisms and therapy.Frontiers in endocrinology · 2026Review
- Negative Impact of p21-Activated Kinase 4-Mediated AMP-Activated Protein Kinase Inhibition on Sarcopenia in Mice and Humans.MedComm · 2025Article
- Cystathionine γ-lyase downregulation promotes liver injury and necroptosis through reprogramming of methionine cycle.Redox report : communications in free radical research · 2025Article
- Pak4-mediated crosstalk between necroptotic macrophages and tendon stem/progenitor cells contributes to traumatic heterotopic ossification formation.Bone research · 2025Article
- PAK4 phosphorylates cyclin-dependent kinase 2 to promote the GExperimental & molecular medicine · 2025Article
- Dietary Polyunsaturated Fatty Acid Deficiency Impairs Renal Lipid Metabolism and Adaptive Response to Proteinuria in Murine Renal Tubules.Nutrients · 2025Article
- p21-Activated Kinase 4 and Ischemic Acute Kidney Injury in Mice and Humans.Journal of the American Society of Nephrology : JASN · 2025Article
- PAK4 promotes the cytoskeletal organization and meiotic maturation via phosphorylating DDX17 in oocyte.Cell communication and signaling : CCS · 2025Article
- Article
- PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.Nature communications · 2024Article
- p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL.Nature metabolism · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid β-oxidation and ketogenesis.
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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.