ArticleThe Journal of cell biology2015
Secreted HHIP1 interacts with heparan sulfate and regulates Hedgehog ligand localization and function.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Systemic Sonic Hedgehog Signaling Links Intestinal Nutrient Sensing With Sex-Specific Type 2 Diabetes Progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Uncovering the role of integrated stress in Alzheimer's disease through single-cell and transcriptomic analysis.Scientific reports · 2026Article
- Dissecting Hhip1 FunctionActa histochemica et cytochemica · 2025Article
- Hedgehog-dependent and hedgehog-independent roles for growth arrest specific 1 in mammalian kidney morphogenesis.Development (Cambridge, England) · 2024Article
- The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.Annual review of biochemistry · 2023Review
- The impact and role of identified long noncoding RNAs in nonalcoholic fatty liver disease: A narrative review.Journal of clinical laboratory analysis · 2023Review
- Circulating HHIP Levels in Women with Insulin Resistance and PCOS: Effects of Physical Activity, Cold Stimulation and Anti-Diabetic Drug Therapy.Journal of clinical medicine · 2023Article
- Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Hedgehog-interacting protein acts in the habenula to regulate nicotine intake.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Unique lingual expression of the Hedgehog pathway antagonist Hedgehog-interacting protein in filiform papillae during homeostasis and ectopic expression in fungiform papillae during Hedgehog signaling inhibition.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Research progress of endothelial-mesenchymal transition in diabetic kidney disease.Journal of cellular and molecular medicine · 2022Review
- Hedgehog pathway modulation by glypican 3-conjugated heparan sulfate.Journal of cell science · 2022Article
- Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling.Nature communications · 2021Article
- Development of a novel label-free all-fiber optofluidic biosensor based on Fresnel reflection and its applications.Analytica chimica acta · 2021Article
- Research Progress on Regulating LncRNAs of Hepatocellular Carcinoma Stem Cells.OncoTargets and therapy · 2021Review
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Neural tube development depends on notochord-derived sonic hedgehog released into the sclerotome.Development (Cambridge, England) · 2020Article
- Proteomics-based screening of the endothelial heparan sulfate interactome reveals that C-type lectin 14a (CLEC14A) is a heparin-binding protein.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Vertebrate Hedgehog (HH) signaling is controlled by several ligand-binding antagonists including Patched-1 (PTCH1), PTCH2, and HH-interacting protein 1 (HHIP1), whose collective action is essential for proper HH pathway activity. However, the molecular mechanisms used by these inhibitors remain poorly understood. In this paper, we investigated the mechanisms underlying HHIP1 antagonism of HH signaling. Strikingly, we found evidence that HHIP1 non-cell-autonomously inhibits HH-dependent neural progenitor patterning and proliferation. Furthermore, this non-cell-autonomous antagonism of HH signaling results from the secretion of HHIP1 that is modulated by cell type-specific interactions with heparan sulfate (HS). These interactions are mediated by an HS-binding motif in the cysteine-rich domain of HHIP1 that is required for its localization to the neuroepithelial basement membrane (BM) to effectively antagonize HH pathway function. Our data also suggest that endogenous, secreted HHIP1 localization to HS-containing BMs regulates HH ligand distribution. Overall, the secreted activity of HHIP1 represents a novel mechanism to regulate HH ligand localization and function during embryogenesis.
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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.