| Literature DB >> 33503403 |
Jiongjia Cheng1, Masanao Tsuda2, Karl Okolotowicz1, Mary Dwyer1, Paul J Bushway3, Alexandre R Colas2, Joseph J Lancman2, Dennis Schade4, Isaac Perea-Gil5, Arne A N Bruyneel5, Jaechol Lee5, Nirmal Vadgama5, Justine Quach1, Wesley L McKeithan6, Travis L Biechele7, Joseph C Wu8, Randall T Moon7, P Duc Si Dong2, Ioannis Karakikes9, John R Cashman2, Mark Mercola10.
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.Entities:
Keywords: Aurora kinases; LEF; TCF; Wnt; ataxia telangiectasia mutated/ATM; homeodomain-interacting protein kinase/HIPK2; p53; β-catenin
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Year: 2021 PMID： 33503403 PMCID： PMC8140986 DOI： 10.1016/j.chembiol.2021.01.001
Source DB: PubMed Journal: Cell Chem Biol ISSN： 2451-9448 Impact factor: 8.116