Minimizing the risk of reporting false positives in large-scale RNAi screens (2006)
Echeverri, Christophe J, Beachy, Philip A, Baum, Buzz, Boutros, Michael, Buchholz, Frank, Chanda, Sumit K, ...
Large-scale RNA interference (RNAi)-based analyses, very much as other 'omic' approaches, have inherent rates of false positives and negatives. The variability in the standards of care applied to...
Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched
Fuse, Naoyuki, Maiti, Tapan, Wang, Baolin, Porter, Jeffery A., Hall, Traci M. Tanaka, Leahy, Daniel J., ...
The amino-terminal signaling domain of the Sonic hedgehog secreted protein (Shh-N), which derives from the Shh precursor through an autoprocessing reaction mediated by the carboxyl-terminal domain,...
Small molecule modulation of Smoothened activity
Chen, James K., Taipale, Jussi, Young, Keith E., Maiti, Tapan, Beachy, Philip A.
Smoothened (Smo), a distant relative of G protein-coupled receptors, mediates Hedgehog (Hh) signaling during embryonic development and can initiate or transmit ligand-independent pathway activation...
Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened
Chen, James K., Taipale, Jussi, Cooper, Michael K., Beachy, Philip A.
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,...
Extensive phosphorylation of Smoothened in Hedgehog pathway activation
Zhang, Chi, Williams, Elizabeth H., Guo, Yurong, Lum, Lawrence, Beachy, Philip A.
The transmembrane protein Smoothened (Smo) is activated in response to the extracellular protein signal, Hedgehog (Hh), and transmits this state of pathway activity into the cell. Previous studies in...
Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly
Maity, Tapan, Fuse, Naoyuki, Beachy, Philip A.
Holoprosencephaly (HPE), a human developmental brain defect, usually is also associated with varying degrees of midline facial dysmorphism. Heterozygous mutations in the Sonic hedgehog (SHH) gene are...
Defective cerebellar response to mitogenic Hedgehog signaling in Down's syndrome mice
Roper, Randall J., Baxter, Laura L., Saran, Nidhi G., Klinedinst, Donna K., Beachy, Philip A., Reeves, Roger H.
Trisomy 21 is the cause of Down's syndrome (DS) which is characterized by a number of phenotypes, including a brain which is small and hypocellular compared to that of euploid individuals. The...
A genomewide screen for components of the RNAi pathway in Drosophila cultured cells
Dorner, Silke, Lum, Lawrence, Kim, Michelle, Paro, Renato, Beachy, Philip A., Green, Rachel
Posttranscriptional silencing by RNAi is initiated by dsRNAs that are processed into siRNAs that ultimately target homologous mRNAs for degradation. We used luciferase reporter constructs and a...
Structure of a heparin-dependent complex of Hedgehog and Ihog
McLellan, Jason S., Yao, Shenqin, Zheng, Xiaoyan, Geisbrecht, Brian V., Ghirlando, Rodolfo, Beachy, Philip A., ...
Hedgehog (Hh) signaling molecules mediate key tissue-patterning events during animal development, and inappropriate activation of Hh signaling in adults has been associated with human cancers....
Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma
Peacock, Craig D., Wang, Qiuju, Gesell, Gregory S., Corcoran-Schwartz, Ian M., Jones, Evan, Kim, Jynho, ...
The cancer stem cell hypothesis suggests that malignant growth depends on a subset of tumor cells with stem cell-like properties of self-renewal. Because hedgehog (Hh) signaling regulates progenitor...