ArticleScientific reports2017
Alkaline ceramidase 2 is a novel direct target of p53 and induces autophagy and apoptosis through ROS generation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Activation of TP53 target genes in the primary response of triple-negative breast cancer cells to doxorubicin treatment.Scientific reports · 2025Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Review
- Robust p53 phenotypes and prospective downstream targets in telomerase-immortalized human cells.Oncotarget · 2025Article
- Sphingolipid metabolism and regulated cell death in malignant melanoma.Apoptosis : an international journal on programmed cell death · 2024Review
- Contribution of sphingomyelin phosphodiesterase acid-like 3B to the proliferation, migration, and invasion of ovarian cancer cells.Translational cancer research · 2024Article
- Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model.Archives of toxicology · 2024Article
- The role of ACER2 in intestinal sphingolipid metabolism and gastrointestinal cancers.Frontiers in immunology · 2024Review
- miR-196a-5p Correlates with Chronic Atrophic Gastritis Progression to Gastric Cancer and Induces Malignant Biological Behaviors of Gastric Cancer Cells by Targeting ACER2.Molecular biotechnology · 2023Article
- Cross-Regulation of the Cellular Redox System, Oxygen, and Sphingolipid Signalling.Metabolites · 2023Review
- ACER2 forms a cold tumor microenvironment and predicts the molecular subtype in bladder cancer: Results from real-world cohorts.Frontiers in genetics · 2023Article
- Review
- Manifold Roles of Ceramide Metabolism in Non-Alcoholic Fatty Liver Disease and Liver Cancer.Advances in experimental medicine and biology · 2022Article
- A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis.International journal of molecular sciences · 2021Review
- Dysregulation of lysophospholipid signaling by p53 in malignant cells and the tumor microenvironment.Cellular signalling · 2021Review
- A Genome-Wide Association Study Identifies Novel Risk Loci for Sarcopenia in a Taiwanese Population.Journal of inflammation research · 2021Article
- Genome-wide transcriptome profiling reveals the mechanisms underlying muscle group-specific phenotypic changes under different raising systems in ducks.Poultry science · 2020Article
- ECRG2, a novel transcriptional target of p53, modulates cancer cell sensitivity to DNA damage.Cell death & disease · 2020Article
- ESRRB regulates glucocorticoid gene expression in mice and patients with acute lymphoblastic leukemia.Blood advances · 2020Article
- Human alkaline ceramidase 2 promotes the growth, invasion, and migration of hepatocellular carcinoma cells via sphingomyelin phosphodiesterase acid-like 3B.Cancer science · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ACER2 is a critical sphingolipid metabolizing enzyme, and has been shown to be remarkably up-regulated following various stimuli such as DNA damage. However, the transcriptional regulatory mechanism of ACER2 gene and its potential role in the regulation of autophagy remain unknown. In this study, we have for the first time identified the human ACER2 gene promoter, and found that human ACER2 transcription is directly regulated by p53 and ACER2 is implicated in the induction of autophagy as well as apoptosis. A series of luciferase reporter assay demonstrated that ACER2 major promoter is located within its first intron where the consensus p53-binding sites exist. Consistently, forced expression of p53 significantly stimulated ACER2 transcription. Notably, p53-mediated autophagy and apoptosis were markedly enhanced by ACER2. Depletion of the essential autophagy gene ATG5 revealed that ACER2-induced autophagy facilitates its effect on apoptosis. Further studies clearly showed that ACER2-mediated autophagy and apoptosis are accompanied by ROS generation. In summary, our present study strongly suggests that ACER2 plays a pivotal role in p53-induced autophagy and apoptosis, and thus might serve as a novel and attractive molecular target for cancer treatment.
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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.