Small-molecule Probe Reveals a Kinase Cascade That Links Stress Signaling to TCF/LEF and Wnt Responsiveness

Overview

Journal Cell Chem Biol

Publisher Cell Press

Specialty Biochemistry

Date 2021 Jan 27

PMID 33503403

Citations 2

Authors

Jiongjia Cheng

Masanao Tsuda

Karl Okolotowicz

Mary Dwyer

Paul J Bushway

Alexandre R Colas

Joseph J Lancman

Dennis Schade

Isaac Perea-Gil

Arne A N Bruyneel

Jaechol Lee

Nirmal Vadgama

Justine Quach

Wesley L McKeithan

Travis L Biechele

Joseph C Wu

Randall T Moon

P Duc Si Dong

Ioannis Karakikes

John R Cashman

Mark Mercola

Affiliations

Soon will be listed here.

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.

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