ArticleMolecular neurobiology2015
Novel link of anti-apoptotic ATF3 with pro-apoptotic CTMP in the ischemic brain.
Article in Molecular neurobiology, 2015. 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, 32 citations in OpenAlex.
- Knockdown of CTMP Enhances Progesterone Sensitivity in Endometrial Cancer by Inhibiting the PI3K/AKT Signaling Pathway.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Correlations between ATF3 polymorphisms and ischemic stroke in Dali, Yunnan Province, as determined by a case-control study.BMC neurology · 2025Article
- Carboxyl Terminal Modulator Protein Induces Cell Senescence and Is Upregulated With Aging by Zic2 in Rats.Journal of cellular physiology · 2025Article
- ATF3 prevents retinal ganglion cell apoptosis and mitigates microglia-mediated neuroinflammation in retinal ischemia-reperfusion injury.Frontiers in immunology · 2025Article
- Overview of carboxyl‑terminal modulator protein 1 and its importance in various metabolic regulations (Review).Molecular medicine reports · 2024Review
- Roles of THEM4 in the Akt pathway: a double-edged sword.Journal of Zhejiang University. Science. B · 2024Review
- The Dual Roles of Activating Transcription Factor 3 (ATF3) in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection Responses.International journal of molecular sciences · 2024Review
- Activating Transcription Factor 3 Diminishes Ischemic Cerebral Infarct and Behavioral Deficit by Downregulating Carboxyl-Terminal Modulator Protein.International journal of molecular sciences · 2023Article
- Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer's disease in metabolically stressed APPswe/PS1dE9 mice.Cell & bioscience · 2021Article
- Clinacanthus nutans Mitigates Neuronal Death and Reduces Ischemic Brain Injury: Role of NF-κB-driven IL-1β Transcription.Neuromolecular medicine · 2021Article
- Development and Validation of a Random Forest Diagnostic Model of Acute Myocardial Infarction Based on Ferroptosis-Related Genes in Circulating Endothelial Cells.Frontiers in cardiovascular medicine · 2021Article
- ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- ATF3 promotes erastin-induced ferroptosis by suppressing system XcCell death and differentiation · 2020Article
- Bioinformatics analyses of differentially expressed genes associated with spinal cord injury: A microarray-based analysis in a mouse model.Neural regeneration research · 2019Article
- Clinacanthus nutans Mitigates Neuronal Apoptosis and Ischemic Brain Damage Through Augmenting the C/EBPβ-Driven PPAR-γ Transcription.Molecular neurobiology · 2018Article
- Carboxyl-Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway.Journal of the American Heart Association · 2018Article
- Expression of DHA-Metabolizing Enzyme Alox15 is Regulated by Selective Histone Acetylation in Neuroblastoma Cells.Neurochemical research · 2018Article
- ATF3 Regulates the Expression of AChE During Stress.Frontiers in molecular neuroscience · 2018Article
- Bioinformatics analysis of gene expression profiling for identification of potential key genes among ischemic stroke.Medicine · 2017Observational
- ATF3 reduces migration capacity by regulation of matrix metalloproteinases via NFCell death discovery · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating transcription factor 3 (ATF3) is a stress-induced transcription factor with diverse functions under disease states in multiple cell types. ATF3 has neuroprotective action against cerebral ischemia, which may involve caspase 3. However, the molecular mechanisms underlying ATF3 regulation of apoptosis are largely unknown. Here, we used gain- and loss-of-function and rescue approaches to demonstrate ATF3 attenuating hypoxic neuronal apoptosis. As well, the protective effect of ATF3 was mediated by downregulation of carboxyl-terminal modulator protein (CTMP), a pro-apoptotic factor that inhibits the anti-apoptotic Akt/PKB cascade. ATF3 (1) downregulated the mRNA and protein levels of CTMP; (2) its temporal expression pattern was reciprocal to that of CTMP; and (3) nuclear localization suggested that ATF3 may regulate CTMP transcription following hypoxic insult. Reporter assays demonstrated that ATF3 suppressed CTMP transcription, whereas ATF3 fusion with VP16, converting ATF3 to transcriptional activator, boosted CTMP transcription. By contrast, NF-κB increased CTMP transcription, and degradation-resistant IκBα decreased CTMP transcription. ChIP assays further confirmed that binding of ATF3 to the ATF/CREB site hindered NF-κB binding to the CTMP promoter, which repressed CTMP expression. Furthermore, CTMP siRNA treatment reduced hypoxic neuronal apoptosis by increasing p-Akt (Ser473) levels and leaving the upstream ATF3 level unchanged. We have identified an endogenous neuroprotective ATF3→CTMP signal cascade that may be a therapeutic target for reducing ischemic brain injury.
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