ArticleProceedings of the National Academy of Sciences of the United States of America2016
Matrix mechanics controls FHL2 movement to the nucleus to activate p21 expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.Circulation research · 2023Pooled it
- Mechanosensitive FHL2 tunes endothelial function via microtubule-actomyosin crosstalk.The EMBO journal · 2026Article
- Mechanical Signaling From ECMs to Nuclear Envelopes in Cell Transitions and Fate Decisions: A Review and Perspective on Adhesion-Niche-Based Anti-EndMT and Anti-EMT.Annals of biomedical engineering · 2026Review
- Article
- HCMV encoded UL84 hijacks FHL2 to suppress type I interferon production and enhance viral replication.PLoS pathogens · 2026Article
- Modeling a mesenchymal cell state by bioprinting for the molecular analysis of dormancy in melanoma.Materials today. Bio · 2025Article
- Article
- FHL2 fused with biotin ligase shuttles between focal adhesions and the nucleus in a myosin II-dependent manner.microPublication biology · 2025Article
- FHL2 in arterial medial calcification in chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Dormancy-inducing 3D engineered matrix uncovers mechanosensitive and drug-protective FHL2-p21 signaling axis.Science advances · 2024Article
- Myosin forces elicit an F-actin structural landscape that mediates mechanosensitive protein recognition.bioRxiv : the preprint server for biology · 2024Article
- fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles.Nature communications · 2024Article
- The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation.International journal of molecular sciences · 2024Review
- The roles of FHL2 as a mechanotransducer for cellular functions in the mechanical environment.Frontiers in cell and developmental biology · 2024Review
- What are the key mechanical mechanisms governing integrin-mediated cell migration in three-dimensional fiber networks?Biomechanics and modeling in mechanobiology · 2023Article
- FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer.Communications biology · 2023Article
- Arp2/3 complex activity is necessary for mouse ESC differentiation, times formative pluripotency, and enables lineage specification.Stem cell reports · 2022Article
- Characterisation of a nucleo-adhesome.Nature communications · 2022Article
- Impact of Treadmill Interval Running on the Appearance of Zinc Finger Protein FHL2 in Bone Marrow Cells in a Rat Model: A Pilot Study.Life (Basel, Switzerland) · 2022Article
- Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces. At the molecular level, shuttling requires a specific tyrosine in FHL2, as well as phosphorylation by active FA kinase (FAK). Thus, we suggest that FHL2 phosphorylation by FAK is a critical, mechanically dependent step in signaling from soft matrices to the nucleus to inhibit cell proliferation by increasing p21 expression.
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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.