ArticleThe Journal of biological chemistry2016
Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- The PERK-GADD45A axis is a key driver of hepatic stellate cell activation.Hepatology communications · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Gadd45B Deficiency Drives Radio-Resistance in BRAFCancers · 2025Article
- Physiological and morphological impact of physical activity and nutritional interventions to offset disuse-induced skeletal muscle atrophy.European journal of translational myology · 2025Article
- The influence of age on cellular senescence in injured versus healthy muscle and its implications on rotator cuff injuries.Journal of shoulder and elbow surgery · 2025Article
- Bioinformatics and machine learning approaches to explore key biomarkers in muscle aging linked to adipogenesis.BMC musculoskeletal disorders · 2025Article
- Analysis of the mechanism of skeletal muscle atrophy from the pathway of decreased protein synthesis.Frontiers in physiology · 2025Review
- Ursolic Acid Induces Beneficial Changes in Skeletal Muscle mRNA Expression and Increases Exercise Participation and Performance in Dogs with Age-Related Muscle Atrophy.Animals : an open access journal from MDPI · 2024Article
- Expression profiling by high-throughput sequencing reveals GADD45, SMAD7, EGR-1 and HOXA3 activation in Myostatin (MSTN) and GDF11 treated myoblasts.Genetics and molecular biology · 2024Article
- GADD45A is a mediator of mitochondrial loss, atrophy, and weakness in skeletal muscle.JCI insight · 2023Article
- Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- GADD45A regulates subcutaneous fat deposition and lipid metabolism by interacting with Stat1.BMC biology · 2023Article
- Loss of FoxOs in muscle increases strength and mitochondrial function during aging.Journal of cachexia, sarcopenia and muscle · 2023Article
- LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle.eLife · 2023Article
- CORP: Gene delivery into murine skeletal muscle using in vivo electroporation.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Review
- Skeletal muscle-specific overexpression of miR-486 limits mammary tumor-induced skeletal muscle functional limitations.Molecular therapy. Nucleic acids · 2022Article
- Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.The Journal of nutrition · 2022Review
- Hemin-Induced Death Models Hemorrhagic Stroke and Is a Variant of Classical Neuronal Ferroptosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- AKT controls protein synthesis and oxidative metabolism via combined mTORC1 and FOXO1 signalling to govern muscle physiology.Journal of cachexia, sarcopenia and muscle · 2022Article
- Reduced Physical Activity Alters the Leucine-Stimulated Translatome in Aged Skeletal Muscle.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level.
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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.