XB-ART-58614
Cell Chem Biol
2021 May 20;285:625-635.e5. doi: 10.1016/j.chembiol.2021.01.001.
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Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.
Cheng J
,
Tsuda M
,
Okolotowicz K
,
Dwyer M
,
Bushway PJ
,
Colas AR
,
Lancman JJ
,
Schade D
,
Perea-Gil I
,
Bruyneel AAN
,
Lee J
,
Vadgama N
,
Quach J
,
McKeithan WL
,
Biechele TL
,
Wu JC
,
Moon RT
,
Si Dong PD
,
Karakikes I
,
Cashman JR
,
Mercola M
.
???displayArticle.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.
???displayArticle.pubmedLink??? 33503403
???displayArticle.pmcLink??? PMC8140986
???displayArticle.link??? Cell Chem Biol
???displayArticle.grants??? [+]
U01 DK105541 NIDDK NIH HHS , R01 HL130840 NHLBI NIH HHS , DP2 DK098092 NIDDK NIH HHS , P01 HL141084 NHLBI NIH HHS , R01 HL113601 NHLBI NIH HHS , R01 HL139679 NHLBI NIH HHS , R00 HL104002 NHLBI NIH HHS , R37 HL059502 NHLBI NIH HHS , R41 CA176931 NCI NIH HHS , R01 HL126527 NHLBI NIH HHS , R43 CA203566 NCI NIH HHS , R01 HL132225 NHLBI NIH HHS , P30 CA030199 NCI NIH HHS , R01 HL146690 NHLBI NIH HHS , R01 HL148827 NHLBI NIH HHS , R01 HL153645 NHLBI NIH HHS
Genes referenced: atm hipk2 tp53
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