ArticleProceedings of the National Academy of Sciences of the United States of America2014
Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- Filamin A phosphorylation at S2152: a molecular switch fueling cancer and neurodegeneration.Cell communication and signaling : CCS · 2026Review
- Identifying potential tear biomarkers in premature infants with retinopathy of prematurity based on proteome and transcriptome analysis.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Article
- Article
- Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications.Neurology international · 2024Review
- Chronic hypoxia for the adaptation of extracellular vesicle phenotype.Scientific reports · 2024Article
- Review
- Charting the importance of filamin A posttranslational modifications.The Biochemical journal · 2024Review
- Role of Filamin A in Growth and Migration of Breast Cancer-Review.Current issues in molecular biology · 2024Review
- Testing calpain inhibition in tumor endothelial cells: novel targetable biomarkers against glioblastoma malignancy.Frontiers in oncology · 2024Article
- Review
- Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice.International journal of molecular medicine · 2023Article
- Calpain-mediated cleavage generates a ZBTB18 N-terminal product that regulates HIF1A signaling and glioblastoma metabolism.iScience · 2022Article
- Calpain-1 mediates vascular remodelling and fibrosis via HIF-1α in hypoxia-induced pulmonary hypertension.Journal of cellular and molecular medicine · 2022Article
- Filamin-A expression in laryngeal squamous cell carcinoma and its clinical significance.Histology and histopathology · 2022Article
- Calpain-2 regulates hypoxia/HIF-induced plasticity toward amoeboid cancer cell migration and metastasis.Current biology : CB · 2022Article
- HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease.Cells · 2021Review
- LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells.Journal of cellular and molecular medicine · 2021Article
- Filamin A Regulates Cardiovascular Remodeling.International journal of molecular sciences · 2021Review
- Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cellular response to hypoxia is regulated by hypoxia-inducible factor-1α and -2α (HIF-1α and -2α). We have discovered that filamin A (FLNA), a large cytoskeletal actin-binding protein, physically interacts with HIF-1α and promotes tumor growth and angiogenesis. Hypoxia induces a calpain-dependent cleavage of FLNA to generate a naturally occurring C-terminal fragment that accumulates in the cell nucleus. This fragment interacts with the N-terminal portion of HIF-1α spanning amino acid residues 1-390 but not with HIF-2α. In hypoxia this fragment facilitates the nuclear localization of HIF-1α, is recruited to HIF-1α target gene promoters, and enhances HIF-1α function, resulting in up-regulation of HIF-1α target gene expression in a hypoxia-dependent fashion. These results unravel an important mechanism that selectively regulates the nuclear accumulation and function of HIF-1α and potentiates angiogenesis and tumor progression.
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