ArticleNature communications2016
p38γ and δ promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 90 citations in OpenAlex.
- Synergistic effects and molecular mechanisms of pirfenidone combined with EGFR-TKIs in non-small cell lung cancer.Translational lung cancer research · 2026Article
- RNAi-mediated p38δ silencing mitigates anthracycline cardiotoxicity in female mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Identification of a resistance-exercise-specific signalling pathway that drives skeletal muscle growth.Nature metabolism · 2025Article
- Deficiency of synaptotagmin-1 aggravates pressure overload-induced cardiac hypertrophy and dysfunction via the p38 MAPK signaling pathway in mice.Human cell · 2025Article
- Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regenerationActa pharmaceutica Sinica. B · 2025Article
- Losmapimod ameliorates doxorubicin-induced cardiotoxicity through attenuating senescence and inflammatory pathways.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- MAPK13 controls structural remodeling and disease after epithelial injury.bioRxiv : the preprint server for biology · 2024Article
- Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.EMBO reports · 2024Article
- Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity.Genome medicine · 2024Article
- MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension.Science advances · 2024Article
- p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.Nature cardiovascular research · 2023Article
- Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease.International journal of molecular sciences · 2023Review
- Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality.JACC. Heart failure · 2023Article
- Review
- Article
- Circadian Governance of Cardiac Growth.Cells · 2022Review
- Signaling cascades in the failing heart and emerging therapeutic strategies.Signal transduction and targeted therapy · 2022Review
- Article
- The complex network of mTOR signalling in the heart.Cardiovascular research · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Disrupted organ growth leads to disease development. Hypertrophy underlies postnatal heart growth and is triggered after stress, but the molecular mechanisms involved in these processes are largely unknown. Here we show that cardiac activation of p38γ and p38δ increases during postnatal development and by hypertrophy-inducing stimuli. p38γ/δ promote cardiac hypertrophy by phosphorylating the mTORC1 and mTORC2 inhibitor DEPTOR, which leads to its degradation and mTOR activation. Hearts from mice lacking one or both kinases are below normal size, have high levels of DEPTOR, low activity of the mTOR pathway and reduced protein synthesis. The phenotype of p38γ/δ(-/-) mice is reverted by overactivation of mTOR with amino acids, shRNA-mediated knockdown of Deptor, or cardiomyocyte overexpression of active p38γ and p38δ. Moreover, in WT mice, heart weight is reduced by cardiac overexpression of DEPTOR. Our results demonstrate that p38γ/δ control heart growth by modulating mTOR pathway through DEPTOR phosphorylation and subsequent degradation.
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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.