ArticleJournal of lipid research2013
Map4k4 suppresses Srebp-1 and adipocyte lipogenesis independent of JNK signaling.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- INSIG1/2 succination mediated by the moonlighting function of ADSL promotes lipogenesis and liver tumorigenesis.Nature communications · 2026Article
- MAP4K signaling pathways in cancer: roles, mechanisms and therapeutic opportunities.Experimental & molecular medicine · 2025Review
- Transcriptome-Based Survival Analysis IdentifiesCancers · 2025Article
- Role of Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Signaling in Liver and Metabolic Diseases.The Journal of pharmacology and experimental therapeutics · 2024Review
- Deciphering the role of alternative splicing as a potential regulator in fat-tail development of sheep: a comprehensive RNA-seq based study.Scientific reports · 2024Review
- Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024Review
- The Combined Partial Knockdown ofAntioxidants (Basel, Switzerland) · 2022Article
- The molecular basis of the dichotomous functionality of MAP4K4 in proliferation and cell motility control in cancer.Frontiers in oncology · 2022Review
- MAP4K4 expression in cardiomyocytes: multiple isoforms, multiple phosphorylations and interactions with striatins.The Biochemical journal · 2021Article
- MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model.Neural regeneration research · 2021Article
- MAP4K Interactome Reveals STRN4 as a Key STRIPAK Complex Component in Hippo Pathway Regulation.Cell reports · 2020Article
- Control of Adipocyte Thermogenesis and Lipogenesis through β3-Adrenergic and Thyroid Hormone Signal Integration.Cell reports · 2020Article
- Article
- RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis.International journal of molecular sciences · 2018Article
- Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.BMC genomics · 2017Article
- Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like ligand datasets.Journal of computer-aided molecular design · 2016Article
- Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases.Trends in endocrinology and metabolism: TEM · 2016Review
- Recent Advances in Adipose mTOR Signaling and Function: Therapeutic Prospects.Trends in pharmacological sciences · 2016Review
- MAP4K4: an emerging therapeutic target in cancer.Cell & bioscience · 2016Review
- Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis.Nature communications · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Adipose tissue lipogenesis is paradoxically impaired in human obesity, promoting ectopic triglyceride (TG) deposition, lipotoxicity, and insulin resistance. We previously identified mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4), a sterile 20 protein kinase reported to be upstream of c-Jun NH2-terminal kinase (JNK) signaling, as a novel negative regulator of insulin-stimulated glucose transport in adipocytes. Using full-genome microarray analysis we uncovered a novel role for Map4k4 as a suppressor of lipid synthesis. We further report here the surprising finding that Map4k4 suppresses adipocyte lipogenesis independently of JNK. Thus, while Map4k4 silencing in adipocytes enhances the expression of lipogenic enzymes, concomitant with increased conversion of (14)C-glucose and (14)C-acetate into TGs and fatty acids, JNK1 and JNK2 depletion causes the opposite effects. Furthermore, high expression of Map4k4 fails to activate endogenous JNK, while Map4k4 depletion does not attenuate JNK activation by tumor necrosis factor α. Map4k4 silencing in cultured adipocytes elevates both the total protein expression and cleavage of sterol-regulated element binding protein-1 (Srebp-1) in a rapamycin-sensitive manner, consistent with Map4k4 signaling via mechanistic target of rapamycin complex 1 (mTORC1). We show Map4k4 depletion requires Srebp-1 upregulation to increase lipogenesis and further show that Map4k4 promotes AMP-protein kinase (AMPK) signaling and the phosphorylation of mTORC1 binding partner raptor (Ser792) to inhibit mTORC1. Our results indicate that Map4k4 inhibits adipose lipogenesis by suppression of Srebp-1 in an AMPK- and mTOR-dependent but JNK-independent mechanism.
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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.