PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-2 (2)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
Document Types
1.  Bili Inhibits Wnt/β-Catenin Signaling by Regulating the Recruitment of Axin to LRP6 
PLoS ONE  2009;4(7):e6129.
Background
Insights into how the Frizzled/LRP6 receptor complex receives, transduces and terminates Wnt signals will enhance our understanding of the control of the Wnt/ß-catenin pathway.
Methodology/Principal Findings
In pursuit of such insights, we performed a genome-wide RNAi screen in Drosophila cells expressing an activated form of LRP6 and a β-catenin-responsive reporter. This screen resulted in the identification of Bili, a Band4.1-domain containing protein, as a negative regulator of Wnt/β-catenin signaling. We found that the expression of Bili in Drosophila embryos and larval imaginal discs significantly overlaps with the expression of Wingless (Wg), the Drosophila Wnt ortholog, which is consistent with a potential function for Bili in the Wg pathway. We then tested the functions of Bili in both invertebrate and vertebrate animal model systems. Loss-of-function studies in Drosophila and zebrafish embryos, as well as human cultured cells, demonstrate that Bili is an evolutionarily conserved antagonist of Wnt/β-catenin signaling. Mechanistically, we found that Bili exerts its antagonistic effects by inhibiting the recruitment of AXIN to LRP6 required during pathway activation.
Conclusions
These studies identify Bili as an evolutionarily conserved negative regulator of the Wnt/β-catenin pathway.
doi:10.1371/journal.pone.0006129
PMCID: PMC2701632  PMID: 19572019
2.  A case study of the reproducibility of transcriptional reporter cell-based RNAi screens in Drosophila 
Genome Biology  2007;8(9):R203.
A second generation dsRNA library was used to re-assess factors that influence the outcome of transcriptional reporter-based whole-genome RNAi screens for the Wnt/Wingless (wg) and Hedgehog (hh)-signaling pathways.
Off-target effects have been demonstrated to be a major source of false-positives in RNA interference (RNAi) high-throughput screens. In this study, we re-assess the previously published transcriptional reporter-based whole-genome RNAi screens for the Wingless and Hedgehog signaling pathways using second generation double-stranded RNA libraries. Furthermore, we investigate other factors that may influence the outcome of such screens, including cell-type specificity, robustness of reporters, and assay normalization, which determine the efficacy of RNAi-knockdown of target genes.
doi:10.1186/gb-2007-8-9-r203
PMCID: PMC2375041  PMID: 17903264

Results 1-2 (2)