Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.

Animals Cells, Cultured Humans Male Molecular Probes / chemistry Protein Serine-Threonine Kinases / metabolism Small Molecule Libraries / chemistry TCF Transcription Factors / antagonists & inhibitors Wnt Signaling Pathway / drug effects Xenopus Zebrafish beta Catenin / antagonists & inhibitors
Aurora kinases LEF TCF Wnt ataxia telangiectasia mutated/ATM homeodomain-interacting protein kinase/HIPK2 p53 β-catenin

Journal

Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030

Informations de publication

Date de publication:
20 05 2021
Historique:
received: 02 04 2020
revised: 02 08 2020
accepted: 04 01 2021
pubmed: 28 1 2021
medline: 11 11 2021
entrez: 27 1 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.chembiol.2021.01.001 PMID: 33503403 PMC: PMC8140986
pubmed: 33503403
pii: S2451-9456(21)00001-5
doi: 10.1016/j.chembiol.2021.01.001
pmc: PMC8140986
mid: NIHMS1667208
pii:
doi:

Substances chimiques

Molecular Probes 0
Small Molecule Libraries 0
TCF Transcription Factors 0
beta Catenin 0
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

625-635.e5

Subventions

Organisme : NIDDK NIH HHS
ID : U01 DK105541
Pays : United States
Organisme : NIDDK NIH HHS
ID : DP2 DK098092
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL141084
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL113601
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139679
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL104002
Pays : United States
Organisme : NHLBI NIH HHS
ID : R37 HL059502
Pays : United States
Organisme : NCI NIH HHS
ID : R41 CA176931
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL126527
Pays : United States
Organisme : NCI NIH HHS
ID : R43 CA203566
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132225
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130840
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148827
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146690
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.R.C. and M.M. have equity in ChemRegen, Inc. and declare no other competing interests. The other authors declare no competing interests. A patent has been issued for the PAWI compounds.

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Auteurs

Jiongjia Cheng (J)

Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.

Masanao Tsuda (M)

Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Karl Okolotowicz (K)

Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.

Mary Dwyer (M)

Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.

Paul J 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.

Alexandre R Colas (AR)

Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Joseph J Lancman (JJ)

Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Dennis 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.

Isaac Perea-Gil (I)

Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.

Arne A N Bruyneel (AAN)

Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.

Jaechol Lee (J)

Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.

Nirmal Vadgama (N)

Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.

Justine Quach (J)

Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.

Wesley L 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.

Travis L Biechele (TL)

Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.

Joseph C 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.

Randall T Moon (RT)

Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.

P Duc Si Dong (PD)

Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Ioannis 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.

John R Cashman (JR)

Sanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Mark 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 University, 240 Pasteur Drive, Palo Alto, CA 94305, USA. Electronic address: mmercola@stanford.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Cellules › Cellules cultivées › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Sondes moléculaires › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Bibliothèques de petites molécules › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription TCF › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Amphibiens › Anura › Pipidae › Xenopus › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Cypriniformes › Cyprinidae › Danio zébré › Small-molecule probe reveals a kinase cascade...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Small-molecule probe reveals a kinase cascade...