ArticleActa crystallographica. Section D, Biological crystallography2013
Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation.
Article in Acta crystallographica. Section D, Biological crystallography, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 66 citations in OpenAlex.
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- Hedgehog-stimulated phosphorylation at multiple sites activates Ci by altering Ci-Ci interfaces without full Suppressor of Fused dissociation.PLoS biology · 2025Article
- Regulatory mechanisms governing GLI proteins in hedgehog signaling.Anatomical science international · 2025Review
- Physiological analysis of the mechanism of Ci transcription factor activation through multiple Fused phosphorylation sites in Hedgehog signal transduction.bioRxiv : the preprint server for biology · 2025Article
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Increasing Sufu gene dosage reveals its unorthodox role in promoting polydactyly and medulloblastoma tumorigenesis.JCI insight · 2024Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- Sonic hedgehog signaling: Alternative splicing and pathogenic role in medulloblastoma.Genes & diseases · 2023Review
- SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer.The Biochemical journal · 2023Article
- Gorlin-Goltz Syndrome: A Case Report and Literature Review withArchives of plastic surgery · 2023Article
- ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1.Life science alliance · 2022Article
- Balancing the length of the distal tip by septins is key for stability and signalling function of primary cilia.The EMBO journal · 2022Article
- Role of the hedgehog signaling pathway in rheumatic diseases: An overview.Frontiers in immunology · 2022Review
- The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time.International journal of molecular sciences · 2021Review
- Hedgehog/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease.Cancers · 2021Review
- Developmental and regenerative paradigms of cilia regulated hedgehog signaling.Seminars in cell & developmental biology · 2021Review
- Hedgehog Signaling in Colorectal Cancer: All in the Stroma?International journal of molecular sciences · 2021Review
- Electrophysiological Study of Visual Pathways in Nevoid Basal Cell Carcinoma Syndrome Patients.Eye and brain · 2021Article
- Suppressor of Fused Inhibits Skin Wound Healing.Advances in wound care · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU-GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU-GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.
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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.