The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened
Open accessAbstract
The steroidal alkaloid cyclopamine has both teratogenic and antitumor activities arising from its ability to specifically block cellular responses to vertebrate Hedgehog signaling. We show here, using photoaffinity and fluorescent derivatives, that this inhibitory effect is mediated by direct binding of cyclopamine to the heptahelical bundle of Smoothened (Smo). Cyclopamine also can reverse the retention of partially misfolded Smo in the endoplasmic reticulum, presumably through binding-mediated effects on protein conformation. These observations reveal the mechanism of cyclopamine's teratogenic and antitumor activities and further suggest a role for small molecules in the physiological regulation of Smo.
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Citations
Cites
Teratogen-Mediated Inhibition of Target Tissue Response to Shh Signaling
Cooper, M. K., Porter, J. A., Young, K. E., & Beachy, P. A. (1998) · Science · doi:10.1126/science.280.5369.1603 · Cited by 848
Self-citationPatched 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 5×
“No analogous protein interactions have been associated with Smo activation, and removal of the Smo CRD does not appear to significantly alter Smo function or its suppression by Ptch (Taipale et al. 2002).”
BackgroundInfluentialSelf-citation
Cited by
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
Hedgehog: functions and mechanisms
Varjosalo, M., & Taipale, J. (2008) · Genes & Development · doi:10.1101/gad.1693608 · Cited by 1,217
Self-citationTissue repair and stem cell renewal in carcinogenesis
Beachy, P. A., Karhadkar, S. S., & Berman, D. M. (2004) · Nature · doi:10.1038/nature03100 · Cited by 1,208
Self-citationHedgehog signalling within airway epithelial progenitors and in small-cell lung cancer
Watkins, D. N., Berman, D. M., Burkholder, S. G., Wang, B., Beachy, P. A., & Baylin, S. B. (2003) · Nature · doi:10.1038/nature01493 · Cited by 1,082
Self-citationClement, V., Sanchez, P., de Tribolet, N., Radovanovic, I., & Ruiz i Altaba, A. (2007) · Current Biology · doi:10.1016/j.cub.2006.11.033 · Cited by 1,050
Metadata
- Authors
- Chen, J. K., Taipale, J., Cooper, M. K., & Beachy, P. A.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-11-01
- Volume
- 16
- Issue
- 21
- Pages
- 2743-2748
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2128801071
- Cited by
- 1,465
- References
- 2
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Chen, J. K., Taipale, J., Cooper, M. K., & Beachy, P. A. (2002). Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes & Development. https://doi.org/10.1101/gad.1025302
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