ArticleMolecular and cellular biology2013
Phosphorylation regulates FOXC2-mediated transcription in lymphatic endothelial cells.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Mechanoreceptor plexin D1 regulates lymphatic valve morphogenesis and lymphedema pathogenesis.The Journal of clinical investigation · 2026Article
- FOXC2 and WT1 regulate transcriptional reprogramming during the podocyte response to injury.JCI insight · 2026Article
- Optic nerve cerebrospinal fluid drainage via lymphatic vessels in its sheath.NPJ microgravity · 2026Article
- MYCT1-IFITM2/3 interaction links endothelial endolysosomal trafficking to white adipose tissue expansion.The Journal of experimental medicine · 2026Article
- The network pharmacology prediction and experiment validation of Astragalus membranaceus for alleviating silicosis fibrosis via decreasing MMP9 and EGFR expression.Scientific reports · 2026Article
- Out"FOX"ing cancer: the implications of FOXC2 as a putative predictive biomarker for cancer immunotherapy.Frontiers in medicine · 2026Article
- Wnt/ERK/CDK4/6 activation in the partial EMT state coordinates mammary cancer stemness with self-renewal and inhibition of differentiation.British journal of cancer · 2025Article
- FOXC2 Promotes Vasculogenic Mimicry in Ovarian Cancer.Cancers · 2022Article
- Progress on Brain and Ocular Lymphatic System.BioMed research international · 2022Review
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- Loss of Primary Cilia Protein IFT20 Dysregulates Lymphatic Vessel Patterning in Development and Inflammation.Frontiers in cell and developmental biology · 2021Article
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- Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2.Frontiers in endocrinology · 2019Article
- Mechanisms of Connexin-Related Lymphedema.Circulation research · 2018Article
- Endothelial immune activation programmes cell-fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4-ERK-FOXC2 signalling.The Journal of physiology · 2018Article
- Distinct transcriptional responses of lymphatic endothelial cells to VEGFR-3 and VEGFR-2 stimulation.Scientific data · 2017Article
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- FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the key mechanisms linking cell signaling and control of gene expression is reversible phosphorylation of transcription factors. FOXC2 is a forkhead transcription factor that is mutated in the human vascular disease lymphedema-distichiasis and plays an essential role in lymphatic vascular development. However, the mechanisms regulating FOXC2 transcriptional activity are not well understood. We report here that FOXC2 is phosphorylated on eight evolutionarily conserved proline-directed serine/threonine residues. Loss of phosphorylation at these sites triggers substantial changes in the FOXC2 transcriptional program. Through genome-wide location analysis in lymphatic endothelial cells, we demonstrate that the changes are due to selective inhibition of FOXC2 recruitment to chromatin. The extent of the inhibition varied between individual binding sites, suggesting a novel rheostat-like mechanism by which expression of specific genes can be differentially regulated by FOXC2 phosphorylation. Furthermore, unlike the wild-type protein, the phosphorylation-deficient mutant of FOXC2 failed to induce vascular remodeling in vivo. Collectively, our results point to the pivotal role of phosphorylation in the regulation of FOXC2-mediated transcription in lymphatic endothelial cells and underscore the importance of FOXC2 phosphorylation in vascular development.
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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.