The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Repression of Smoothened by Patched-Dependent (Pro-)Vitamin D3 Secretion
Open accessAbstract
The developmentally important hedgehog (Hh) pathway is activated by binding of Hh to patched (Ptch1), releasing smoothened (Smo) and the downstream transcription factor glioma associated (Gli) from inhibition. The mechanism behind Ptch1-dependent Smo inhibition remains unresolved. We now show that by mixing Ptch1-transfected and Ptch1 small interfering RNA-transfected cells with Gli reporter cells, Ptch1 is capable of non-cell autonomous repression of Smo. The magnitude of this non-cell autonomous repression of Smo activity was comparable to the fusion of Ptch1-transfected cell lines and Gli reporter cell lines, suggesting that it is the predominant mode of action. CHOD-PAP analysis of medium conditioned by Ptch1-transfected cells showed an elevated 3beta-hydroxysteroid content, which we hypothesized to mediate the Smo inhibition. Indeed, the inhibition of 3beta-hydroxysteroid synthesis impaired Ptch1 action on Smo, whereas adding the 3beta-hydroxysteroid (pro-)vitamin D3 to the medium effectively inhibited Gli activity. Vitamin D3 bound to Smo with high affinity in a cyclopamine-sensitive manner. Treating zebrafish embryos with vitamin D3 mimicked the smo(-/-) phenotype, confirming the inhibitory action in vivo. Hh activates its signalling cascade by inhibiting Ptch1-dependent secretion of the 3beta-hydroxysteroid (pro-)vitamin D3. This action not only explains the seemingly contradictory cause of Smith-Lemli-Opitz syndrome (SLOS), but also establishes Hh as a unique morphogen, because binding of Hh on one cell is capable of activating Hh-dependent signalling cascades on other cells.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Altered Neural Cell Fates and Medulloblastoma in Mouse patched Mutants
Goodrich, L. V., Milenković, L., Higgins, K. M., & Scott, M. P. (1997) · Science · doi:10.1126/science.277.5329.1109 · Cited by 1,696
Vertebrate Smoothened functions at the primary cilium
Corbit, K. C., Aanstad, P., Singla, V., Norman, A. R., Stainier, D. Y. R., & Reiter, J. F. (2005) · Nature · doi:10.1038/nature04117 · Cited by 1,481
Patched acts catalytically to suppress the activity of Smoothened
Taipale, J., Cooper, M. K., Maiti, T., & Beachy, P. A. (2002) · Nature · doi:10.1038/nature00989 · Cited by 794 · cited 1×
“Because Ptch1 and Smo do not unambiguously show physical association and because Ptch1 can inhibit Smo substoichiometrically, direct binding of Ptch1 to Smo as shown in Figures 1B, columns 1 and 2, seems an unlikely mechanism of inhibition [9].”
Sasaki, H., Nishizaki, Y., Hui, C.-C., Nakafuku, M., & Kondoh, H. (1999) · Development · doi:10.1242/dev.126.17.3915 · Cited by 715
Cited by
Hedgehog: functions and mechanisms
Varjosalo, M., & Taipale, J. (2008) · Genes & Development · doi:10.1101/gad.1693608 · Cited by 1,217
Basal cell carcinomas: attack of the hedgehog
Epstein, E. H. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2503 · Cited by 834
Dessaud, E., McMahon, A. P., & Briscoe, J. (2008) · Development · doi:10.1242/dev.009324 · Cited by 734
Malformation syndromes caused by disorders of cholesterol synthesis
Porter, F. D., & Herman, G. E. (2011) · Journal of Lipid Research · doi:10.1194/jlr.r009548 · Cited by 473
The Hedgehog Signal Transduction Network
Robbins, D. J., Fei, D. L., & Riobo, N. A. (2012) · Science Signaling · doi:10.1126/scisignal.2002906 · Cited by 419
Wang, J., Guo, L.-P., Chen, L.-Z., Zeng, Y.-X., & Lu, S. H. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4343 · Cited by 363
Hedgehog Signaling in Development and Homeostasis of the Gastrointestinal Tract
van den Brink, G. R. (2007) · Physiological Reviews · doi:10.1152/physrev.00054.2006 · Cited by 301
Orchestrating ontogenesis: variations on a theme by sonic hedgehog
Ingham, P. W., & Placzek, M. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1969 · Cited by 271
Vitamin D and the skin: Physiology and pathophysiology
Bikle, D. D. (2012) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9194-0 · Cited by 260
G-protein-coupled receptors, Hedgehog signaling and primary cilia
Mukhopadhyay, S., & Rohatgi, R. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.05.002 · Cited by 142
Shifting paradigms in Hedgehog signaling
Wang, Y., McMahon, A. P., & Allen, B. L. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.02.005 · Cited by 124
Tang, J. Y., Fu, T., LeBlanc, E., Manson, J. E., Feldman, D., Linos, E., Vitolins, M. Z., Zeitouni, N. C., Larson, J., & Stefanick, M. L. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.5967 · Cited by 117
Vitamin D receptor, a tumor suppressor in skin
Bikle, D. D. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0367 · Cited by 101
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception
Yue, S., Tang, L.-Y., Tang, Y., Tang, Y., Shen, Q.-H., Ding, J., Chen, Y., Zhang, Z., Yu, T.-T., Zhang, Y. E., et al. (2014) · eLife · doi:10.7554/elife.02555 · Cited by 94
Song, E. J., Gordon-Thomson, C., Cole, L., Stern, H., Halliday, G. M., Damian, D. L., Reeve, V. E., & Mason, R. S. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2012.11.003 · Cited by 65
The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time
Effendi, W. I., & Nagano, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010171 · Cited by 59
Mimeault, M., & Batra, S. K. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00885.x · Cited by 38
Sunlight, Vitamin D, and Xeroderma Pigmentosum
Martens, M. C., Emmert, S., & Boeckmann, L. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-46227-7_16 · Cited by 24
Non-cell-autonomous signaling by Shh in tumors: challenges and opportunities for therapeutic targets
Bijlsma, M. F., & Roelink, H. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.497488 · Cited by 11
Self-citation
Metadata
- Authors
- Bijlsma, M. F., Spek, C. A., Zivkovic, D., van de Water, S., Rezaee, F., & Peppelenbosch, M. P.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2006-07-18
- Volume
- 4
- Issue
- 8
- Pages
- e232
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2127168458
- Cited by
- 314
- References
- 4
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
