ArticleCell research2012
Cleavage of serum response factor mediated by enteroviral protease 2A contributes to impaired cardiac function.
Article in Cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Desmin mutations in cardiomyocytes increase susceptibility to coxsackievirus B3 infection by impairing antiviral IFN-β response and upregulating viral receptors expression.Stem cell research & therapy · 2026Article
- Identification of the proteolytic signature in CVB3-infected cells.Journal of virology · 2024Article
- Micropeptides: origins, identification, and potential role in metabolism-related diseases.Journal of Zhejiang University. Science. B · 2023Review
- Mitochondria Dysfunction at the Heart of Viral Myocarditis: Mechanistic Insights and Therapeutic Implications.Viruses · 2023Review
- Enhanced genomic stability of new miRNA-regulated oncolytic coxsackievirus B3.Molecular therapy oncolytics · 2022Article
- SRF: a seriously responsible factor in cardiac development and disease.Journal of biomedical science · 2022Review
- Review
- Innate immune evasion mediated by picornaviral 3C protease: Possible lessons for coronaviral 3C-like protease?Reviews in medical virology · 2021Review
- MicroRNA Modification of Coxsackievirus B3 Decreases Its Toxicity, while Retaining Oncolytic Potency against Lung Cancer.Molecular therapy oncolytics · 2020Article
- SG formation relies on eIF4GI-G3BP interaction which is targeted by picornavirus stress antagonists.Cell discovery · 2019Article
- Toll-Like Receptor 3 Is Involved in Detection of Enterovirus A71 Infection and Targeted by Viral 2A Protease.Viruses · 2018Article
- Approaches to identify and characterize microProteins and their potential uses in biotechnology.Cellular and molecular life sciences : CMLS · 2018Review
- The Nrf2 Signaling in Retinal Ganglion Cells under Oxidative Stress in Ocular Neurodegenerative Diseases.International journal of biological sciences · 2018Review
- Phosphorylation and degradation of αB-crystallin during enterovirus infection facilitates viral replication and induces viral pathogenesis.Oncotarget · 2017Article
- Structures and Corresponding Functions of Five Types of Picornaviral 2A Proteins.Frontiers in microbiology · 2017Review
- Cleavage of Grb2-Associated Binding Protein 2 by Viral Proteinase 2A duringFrontiers in cellular and infection microbiology · 2017Article
- Enteroviral proteases: structure, host interactions and pathogenicity.Reviews in medical virology · 2016Review
- Serum Response Factor Protects Retinal Ganglion Cells Against High-Glucose Damage.Journal of molecular neuroscience : MN · 2016Article
- Cleavage of DAP5 by coxsackievirus B3 2A protease facilitates viral replication and enhances apoptosis by altering translation of IRES-containing genes.Cell death and differentiation · 2016Article
- Cytoplasmic translocation, aggregation, and cleavage of TDP-43 by enteroviral proteases modulate viral pathogenesis.Cell death and differentiation · 2015Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Enteroviral infection can lead to dilated cardiomyopathy (DCM), which is a major cause of cardiovascular mortality worldwide. However, the pathogenetic mechanisms have not been fully elucidated. Serum response factor (SRF) is a cardiac-enriched transcription regulator controlling the expression of a variety of target genes, including those involved in the contractile apparatus and immediate early response, as well as microRNAs that silence the expression of cardiac regulatory factors. Knockout of SRF in the heart results in downregulation of cardiac contractile gene expression and development of DCM. The goal of this study is to understand the role of SRF in enterovirus-induced cardiac dysfunction and progression to DCM. Here we report that SRF is cleaved following enteroviral infection of mouse heart and cultured cardiomyocytes. This cleavage is accompanied by impaired cardiac function and downregulation of cardiac-specific contractile and regulatory genes. Further investigation by antibody epitope mapping and site-directed mutagenesis demonstrates that SRF cleavage occurs at the region of its transactivation domain through the action of virus-encoded protease 2A. Moreover, we demonstrate that cleavage of SRF dissociates its transactivation domain from DNA-binding domain, resulting in the disruption of SRF-mediated gene transactivation. In addition to loss of functional SRF, finally we report that the N-terminal fragment of SRF cleavage products can also act as a dominant-negative transcription factor, which likely competes with the native SRF for DNA binding. Our results suggest a mechanism by which virus infection impairs heart function and may offer a new therapeutic strategy to ameliorate myocardial damage and progression to DCM.
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