ArticleAutophagy2018
Crosstalk between lysine methylation and phosphorylation of ATG16L1 dictates the apoptosis of hypoxia/reoxygenation-induced cardiomyocytes.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Crosstalk between ubiquitination and other post-translational modifications in cardiovascular diseases.iScience · 2026Review
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- The emerging paradigms of SETD family enzymes as epigenetic regulators of the immune response in inflammatory diseases.Frontiers in immunology · 2026Review
- Role and research progress of histone modification in cardiovascular diseases (Review).Experimental and therapeutic medicine · 2025Review
- cIAP2-mediated IGF2BP2 ubiquitination and degradation regulate cardiomyocyte apoptosis via stabilizing mCell biology and toxicology · 2025Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025Review
- ZDHHC7-mediatedAutophagy · 2024Article
- LSD1 Demethylates and Destabilizes Autophagy Protein LC3B in Ovarian Cancer.Biomolecules · 2024Article
- Research progress on post-translational modification of proteins and cardiovascular diseases.Cell death discovery · 2023Review
- iHypoxia: An Integrative Database of Protein Expression Dynamics in Response to Hypoxia in Animals.Genomics, proteomics & bioinformatics · 2023Article
- Advances in epigenetic modifications of autophagic process in pulmonary hypertension.Frontiers in immunology · 2023Review
- Plasma-derived extracellular vesicles transfer microRNA-130a-3p to alleviate myocardial ischemia/reperfusion injury by targeting ATG16L1.Cell and tissue research · 2022Article
- The histone demthylase KDM3A protects the myocardium from ischemia/reperfusion injury via promotion of ETS1 expression.Communications biology · 2022Article
- How Protein Methylation Regulates Steroid Receptor Function.Endocrine reviews · 2022Review
- Article
- Methionine oxidation of CLK4 promotes the metabolic switch and redox homeostasis in esophageal carcinoma via inhibiting MITF selective autophagy.Clinical and translational medicine · 2022Article
- Arginine methyltransferase PRMT5 methylates and stabilizes KLF5 via decreasing its phosphorylation and ubiquitination to promote basal-like breast cancer.Cell death and differentiation · 2021Article
- Hypoxia-induced acetylation of PAK1 enhances autophagy and promotes brain tumorigenesis via phosphorylating ATG5.Autophagy · 2021Article
- The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties.Signal transduction and targeted therapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-translational modifications of autophagy-related (ATG) genes are necessary to modulate their functions. However, ATG protein methylation and its physiological role have not yet been elucidated. The methylation of non-histone proteins by SETD7, a SET domain-containing lysine methyltransferase, is a novel regulatory mechanism to control cell protein function in response to various cellular stresses. Here we present evidence that the precise activity of ATG16L1 protein in hypoxia/reoxygenation (H/R)-treated cardiomyocytes is regulated by a balanced methylation and phosphorylation switch. We first show that H/R promotes autophagy and decreases SETD7 expression, whereas autophagy inhibition by 3-MA increases SETD7 level in cardiomyocytes, implying a tight correlation between autophagy and SETD7. Then we demonstrate that SETD7 methylates ATG16L1 at lysine 151 while KDM1A/LSD1 (lysine demethylase 1A) removes this methyl mark. Furthermore, we validate that this methylation at lysine 151 impairs the binding of ATG16L1 to the ATG12-ATG5 conjugate, leading to inhibition of autophagy and increased apoptosis in H/R-treated cardiomyocytes. However, the cardiomyocytes with shRNA-knocked down SETD7 or inhibition of SETD7 activity by a small molecule chemical, display increased autophagy and decreased apoptosis following H/R treatment. Additionally, methylation at lysine 151 inhibits phosphorylation of ATG16L1 at S139 by CSNK2 which was previously shown to be critical for autophagy maintenance, and vice versa. Together, our findings define a novel modification of ATG16L1 and highlight the importance of an ATG16L1 phosphorylation-methylation switch in determining the fate of H/R-treated cardiomyocytes.
Indexed as
Identifiers
What OpenQuestion holds
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.