PUBLICATION
Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness
- Authors
- Cheng, J., Tsuda, M., Okolotowicz, K., Dwyer, M., Bushway, P.J., Colas, A.R., Lancman, J.J., Schade, D., Perea-Gil, I., Bruyneel, A.A.N., Lee, J., Vadgama, N., Quach, J., McKeithan, W.L., Biechele, T.L., Wu, J.C., Moon, R.T., Si Dong, P.D., Karakikes, I., Cashman, J.R., Mercola, M.
- ID
- ZDB-PUB-211111-12
- Date
- 2021
- Source
- Cell chemical biology 28: 625-635.e5 (Journal)
- Registered Authors
- Lancman, Joseph, Moon, Randall T.
- Keywords
- Aurora kinases, LEF, TCF, Wnt, ataxia telangiectasia mutated/ATM, homeodomain-interacting protein kinase/HIPK2, p53, β-catenin
- MeSH Terms
-
- Animals
- Cells, Cultured
- Humans
- Male
- Molecular Probes/chemistry
- Molecular Probes/pharmacology*
- Protein Serine-Threonine Kinases/metabolism*
- Small Molecule Libraries/chemistry
- Small Molecule Libraries/pharmacology*
- TCF Transcription Factors/antagonists & inhibitors*
- TCF Transcription Factors/genetics
- TCF Transcription Factors/metabolism
- Wnt Signaling Pathway/drug effects
- Xenopus
- Zebrafish
- beta Catenin/antagonists & inhibitors*
- beta Catenin/genetics
- beta Catenin/metabolism
- PubMed
- 33503403 Full text @ Cell Chem Biol
Citation
Cheng, J., Tsuda, M., Okolotowicz, K., Dwyer, M., Bushway, P.J., Colas, A.R., Lancman, J.J., Schade, D., Perea-Gil, I., Bruyneel, A.A.N., Lee, J., Vadgama, N., Quach, J., McKeithan, W.L., Biechele, T.L., Wu, J.C., Moon, R.T., Si Dong, P.D., Karakikes, I., Cashman, J.R., Mercola, M. (2021) Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness. Cell chemical biology. 28:625-635.e5.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping