Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Export

@article{citeulike:201588, abstract = {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.}, address = {Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, author = {Chen, J. K. and Taipale, J. and Cooper, M. K. and Beachy, P. A.}, citeulike-article-id = {201588}, citeulike-linkout-0 = {http://dx.doi.org/10.1101/gad.1025302}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12414725}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12414725}, day = {1}, doi = {10.1101/gad.1025302}, issn = {0890-9369}, journal = {Genes Dev}, keywords = {cyclopamine, hedgehog, smo}, month = {November}, number = {21}, pages = {2743--2748}, posted-at = {2005-05-16 18:07:11}, priority = {2}, title = {Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened.}, url = {http://dx.doi.org/10.1101/gad.1025302}, volume = {16}, year = {2002} }

TY - JOUR ID - citeulike:201588 L3 - citeulike-article-id:201588 N2 - 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. IS - 21 JF - Genes Dev SN - 0890-9369 AD - Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. EP - 2748 TI - Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. VL - 16 SP - 2743 KW - cyclopamine KW - hedgehog KW - smo AU - Chen, JK AU - Taipale, J AU - Cooper, MK AU - Beachy, PA PY - 2002/11/01/ UR - http://dx.doi.org/10.1101/gad.1025302 ER -