ArticleThe Journal of biological chemistry2012
Precise regulation of porcupine activity is required for physiological Wnt signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 120 citations in OpenAlex.
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- The Developmental Landscape of Children With Uveal Coloboma and Its Relationship With Clinical Phenotype and Genetics.American journal of ophthalmology · 2026Article
- Structural basis for Porcupine inhibition.Communications chemistry · 2025Article
- Long-Term Hypoxia Upregulates Wnt and TGFβ1 Signaling in Eccrine Sweat Gland Cells In Vitro.International journal of molecular sciences · 2025Article
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- Acyltransferases that Modify Cell Surface Polymers Across the Membrane.Biochemistry · 2025Review
- Nuclear porcupine mediates XRCC6/Ku70 S-palmitoylation in the DNA damage response.Experimental hematology & oncology · 2024Article
- A cochlear progenitor pool influences patterning of the mammalian sensory epithelium via MYBL2.Development (Cambridge, England) · 2024Article
- The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.Genes & diseases · 2024Review
- Engineering of TurboID-Wingless for the identification of Wingless interactors throughmicroPublication biology · 2024Article
- Epigenetic control of pancreatic cancer metastasis.Cancer metastasis reviews · 2023Review
- Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche.Cell stem cell · 2023Article
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- Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.Journal of tissue engineering and regenerative medicine · 2022Review
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- Canonical Wnt Signaling in the Pathology of Iron Overload-Induced Oxidative Stress and Age-Related Diseases.Oxidative medicine and cellular longevity · 2022Review
- Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors.Nature communications · 2021Article
- Spatial and temporal expression of PORCN is highly dynamic in the developing mouse cochlea.Gene expression patterns : GEP · 2021Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gradients of diverse Wnt proteins regulate development, renewal, and differentiation. Porcupine (PORCN) is a membrane-bound O-acyltransferase that is required for post-translational modification of all Wnts to enable their transport, secretion, and activity. Mutations in PORCN are associated with focal dermal hypoplasia (FDH), whereas gene deletion causes embryonic lethality in mice. To study the protein in more detail, zinc finger nucleases were used to edit the PORCN genomic locus, establishing two HT1080 fibrosarcoma clones null for PORCN activity that facilitate the study of PORCN structure and function. We establish that PORCN is a key non-redundant node for the regulation of global Wnt signaling because PORCN null cells are completely incapable of autocrine Wnt signaling. The strength of Wnt signaling is exquisitely sensitive to PORCN expression, with a dynamic range of at least 3 orders of magnitude, suggesting that PORCN activity is a key modulator of all Wnt ligand activity. Consistent with this, we find that multiple FDH-associated mutants have only subtle alterations in enzyme activity yet are associated with a severe FDH phenotype. These studies support an essential regulatory role of PORCN in shaping Wnt signaling gradients.
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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.