ArticleEMBO reports2024
The transcription factor PAX5 activates human LINE1 retrotransposons to induce cellular senescence.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- LINE-1 Epigenetic Repression and Regulation of Immunity.Viruses · 2026Review
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Quantitative Control of Transposable Elements: From Genome Plasticity to Immune Regulatory Circuits.Cell biochemistry and function · 2026Review
- LINC00312 increases gemcitabine sensitivity in nasopharyngeal carcinoma by recruiting PABPC1 and modulating PAX5-mediated transcription of LPLUNC1.NPJ precision oncology · 2026Article
- LINE-1 retrotransposons: Multifaceted functions and regulatory mechanisms in health and disease.Molecular therapy. Nucleic acids · 2026Review
- Loss of SETDB1-mediated H3K9me3 in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons.Nucleic acids research · 2026Article
- Targeting age-related LINE-1 activation alleviates cardiac aging.Nature aging · 2026Article
- The Role of Non-LTR Retrotransposons in Sterile Inflammation: Mechanisms and Therapeutic Potential.Biomedicines · 2026Review
- Natural Products as Anti-Senescence-Associated Secretory Phenotype (SASP) Agents.Current medicinal chemistry · 2026Review
- Systemic LINE-1 RNA in Plasma Extracellular Vesicles Drives Neuroinflammation and Cognitive Dysfunction via cGAS-STING Pathway in Aging.Aging cell · 2026Article
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- LINE-1 retrotransposition in a mouse TDP-43 model of neurodegeneration marks motor cortex neurons for cell-intrinsic and cell non-autonomous programmed cell death.PLoS genetics · 2025Article
- ETNet: an interpretable transformer framework for enhancer-enhancer interaction prediction with cross-context transferability.Briefings in bioinformatics · 2025Article
- Antagonistic regulation of LINE-1/Alu elements and their repressor APOBEC3B in cellular senescence.Mobile DNA · 2025Article
- An endogenous retroviral element co-opts an upstream regulatory sequence to achieve somatic expression and mobility.Nucleic acids research · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
As a hallmark of senescent cells, the derepression of Long Interspersed Elements 1 (LINE1) transcription results in accumulated LINE1 cDNA, which triggers the secretion of the senescence-associated secretory phenotype (SASP) and paracrine senescence in a cGAS-STING pathway-dependent manner. However, transcription factors that govern senescence-associated LINE1 reactivation remain ill-defined. Here, we predict several transcription factors that bind to human LINE1 elements to regulate their transcription by analyzing the conserved binding motifs in the 5'-untranslated regions (UTR) of the commonly upregulated LINE1 elements in different types of senescent cells. Further analysis reveals that PAX5 directly binds to LINE1 5'-UTR and the binding is enhanced in senescent cells. The enrichment of PAX5 at the 5'-UTR promotes cellular senescence and SASP by activating LINE1. We also demonstrate that the longevity gene SIRT6 suppresses PAX5 transcription by directly binding to the PAX5 promoter, and overexpressing PAX5 abrogates the suppressive effect of SIRT6 on stress-dependent cellular senescence. Our work suggests that PAX5 could serve as a potential target for drug development aiming to suppress LINE1 activation and treat senescence-associated diseases.
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