Bachelor of Science, University Of London (2009)
Master of Science, University Of London (2010)
Doctor of Philosophy, University College London (2018)
Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.
Cell chemical biology
Wnt signaling plays a central role in tissue maintenance and cancer. Wnt activates downstream genes through β-catenin, which interacts with TCF/LEF transcription factors. A major question is how this signaling is coordinated relative to tissue organization and renewal. We used a recently described class of small molecules that binds tubulin to reveal a molecular cascade linking stress signaling through ATM, HIPK2, and p53 to the regulation of TCF/LEF transcriptional activity. These data suggest a mechanism by which mitotic and genotoxic stress can indirectly modulate Wnt responsiveness to exert coherent control over cell shape and renewal. These findings have implications for understanding tissue morphogenesis and small-molecule anticancer therapeutics.
View details for DOI 10.1016/j.chembiol.2021.01.001
View details for PubMedID 33503403