ArticleCell death and differentiation2015
Nesprin-2-dependent ERK1/2 compartmentalisation regulates the DNA damage response in vascular smooth muscle cell ageing.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma.Cancer medicine · 2020Pooled it
- Exploring the Role of Nesprin1 in isoproterenol-induced heart failure: Insights into pathogenesis and therapeutic implications.PloS one · 2026Article
- Decoding Vascular Senescence: Cellular Insights and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Arterial origin-dependent susceptibility of vascular smooth muscle cells to prelamin A-induced senescence and rescue by umbilical artery-derived decellularized extracellular matrix.International journal of clinical and experimental pathology · 2026Article
- Evidence that G-quadruplexes form in pathogenic fungi and represent promising antifungal targets.EMBO molecular medicine · 2025Article
- The dual guardians of cellular stability: exploring nesprin and lamin in senescence.Cell death & disease · 2025Review
- A distinct isoform of Msp300 (nesprin) organizes the perinuclear microtubule-organizing center in adipocytes.Molecular biology of the cell · 2025Article
- The LINC Complex Regulates Tendon Elastic Modulus, Collagen Crimp, and Lateral Expansion During Early Postnatal Development.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Feeling the force from within - new tools and insights into nuclear mechanotransduction.Journal of cell science · 2025Review
- Filamentous nuclear actin regulation of PML NBs during the DNA damage response is deregulated by prelamin A.Cell death & disease · 2022Article
- Lamin A to Z in normal aging.Aging · 2022Article
- LINCing Senescence and Nuclear Envelope Changes.Cells · 2022Review
- BMP9 reduces age-related bone loss in mice by inhibiting osteoblast senescence through Smad1-Stat1-P21 axis.Cell death discovery · 2022Article
- Using Polyacrylamide Hydrogels to Model Physiological Aortic Stiffness Reveals that Microtubules Are Critical Regulators of Isolated Smooth Muscle Cell Morphology and Contractility.Frontiers in pharmacology · 2022Article
- Nuclear Mechanosensation and Mechanotransduction in Vascular Cells.Frontiers in cell and developmental biology · 2022Review
- Vascular Calcification Mechanisms: Updates and Renewed Insight into Signaling Pathways Involved in High Phosphate-Mediated Vascular Smooth Muscle Cell Calcification.Biomedicines · 2021Review
- SUN1/2 Are Essential for RhoA/ROCK-Regulated Actomyosin Activity in Isolated Vascular Smooth Muscle Cells.Cells · 2020Article
- The functional importance of lamins, actin, myosin, spectrin and the LINC complex in DNA repair.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Calcium Signaling and Tissue Calcification.Cold Spring Harbor perspectives in biology · 2019Review
- Integrative genomic analysis identifies associations of molecular alterations to APOBEC and BRCA1/2 mutational signatures in breast cancer.Molecular genetics & genomic medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Prelamin A accumulation and persistent DNA damage response (DDR) are hallmarks of vascular smooth muscle cell (VSMC) ageing and dysfunction. Although prelamin A is proposed to interfere with DNA repair, our understanding of the crosstalk between prelamin A and the repair process remains limited. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) have emerged as key players in the DDR and are known to enhance ataxia telangiectasia-mutated protein (ATM) activity at DNA lesions, and in this study, we identified a novel relationship between prelamin A accumulation and ERK1/2 nuclear compartmentalisation during VSMC ageing. We show both prelamin A accumulation and increased DNA damage occur concomitantly, before VSMC replicative senescence, and induce the localisation of ERK1/2 to promyelocytic leukaemia protein nuclear bodies (PML NBs) at the sites of DNA damage via nesprin-2 and lamin A interactions. Importantly, VSMCs treated with DNA damaging agents also displayed prelamin A accumulation and ERK compartmentalisation at PML NBs, suggesting that prelamin A and nesprin-2 are novel components of the DDR. In support of this, disruption of ERK compartmentalisation at PML NBs, by either depletion of nesprin-2 or lamins A/C, resulted in the loss of ATM from DNA lesions. However, ATM signalling and DNA repair remained intact after lamins A/C depletion, whereas nesprin-2 disruption ablated downstream Chk2 activation and induced genomic instability. We conclude that lamins A/C and PML act as scaffolds to organise DNA-repair foci and compartmentalise nesprin-2/ERK signalling. However, nesprin-2/ERK signalling fidelity, but not their compartmentalisation at PML NBs, is essential for efficient DDR in VSMCs.
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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.