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Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.
Cheng, Jiongjia; Tsuda, Masanao; Okolotowicz, Karl; Dwyer, Mary; Bushway, Paul J; Colas, Alexandre R; Lancman, Joseph J; Schade, Dennis; Perea-Gil, Isaac; Bruyneel, Arne A N; Lee, Jaechol; Vadgama, Nirmal; Quach, Justine; McKeithan, Wesley L; Biechele, Travis L; Wu, Joseph C; Moon, Randall T; Si Dong, P Duc; Karakikes, Ioannis; Cashman, John R; Mercola, Mark.
Afiliação
  • Cheng J; Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
  • Tsuda M; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Okolotowicz K; Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
  • Dwyer M; Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
  • Bushway PJ; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; University of California, San Diego, San Diego, CA 92093, USA.
  • Colas AR; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Lancman JJ; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Schade D; Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA; Institute of Pharmacy, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, Kiel, Germany.
  • Perea-Gil I; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
  • Bruyneel AAN; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
  • Lee J; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
  • Vadgama N; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
  • Quach J; Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
  • McKeithan WL; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
  • Biechele TL; Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.
  • Wu JC; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA; Department of Medicine, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
  • Moon RT; Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.
  • Si Dong PD; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Karakikes I; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA; Department of Cardiothoracic Surgery, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
  • Cashman JR; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Mercola M; Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; University of California, San Diego, San Diego, CA 92093, USA; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA; Department of Medicine, Stanford Univ
Cell Chem Biol ; 28(5): 625-635.e5, 2021 05 20.
Article em En | MEDLINE | ID: mdl-33503403
ABSTRACT
Wnt signaling plays a central role in tissue maintenance and cancer. Wnt activates downstream genes through ß-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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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Sondas Moleculares / Proteínas Serina-Treonina Quinases / Beta Catenina / Fatores de Transcrição TCF / Bibliotecas de Moléculas Pequenas Limite: Animals / Humans / Male Idioma: En Revista: Cell Chem Biol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Sondas Moleculares / Proteínas Serina-Treonina Quinases / Beta Catenina / Fatores de Transcrição TCF / Bibliotecas de Moléculas Pequenas Limite: Animals / Humans / Male Idioma: En Revista: Cell Chem Biol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos