Can We Pharmacologically Target Dishevelled: The Key Signal Transducer in the Wnt Pathways?
Casein kinase 1
DIX oligomerization
Dishevelled
PDZ inhibitors
Wnt signalling-related diseases
Journal
Handbook of experimental pharmacology
ISSN: 0171-2004
Titre abrégé: Handb Exp Pharmacol
Pays: Germany
ID NLM: 7902231
Informations de publication
Date de publication:
2021
2021
Historique:
pubmed:
13
8
2021
medline:
3
11
2021
entrez:
12
8
2021
Statut:
ppublish
Résumé
Dishevelled (DVL) is the central signal transducer in both Wnt/β-catenin-dependent and independent signalling pathways. DVL is required to connect receptor complexes and downstream effectors. Since proximal Wnt pathway components and DVL itself are upregulated in many types of cancer, DVL represents an attractive therapeutic target in the Wnt-addicted cancers and other disorders caused by aberrant Wnt signalling. Here, we discuss progress in several approaches for the modulation of DVL function and hence inhibition of the Wnt signalling. Namely, we sum up the potential of modulation of enzymes that control post-translational modification of DVL - such as inhibition of DVL kinases or promotion of DVL ubiquitination and degradation. In addition, we discuss research directions that can take advantage of direct interaction with the protein domains essential for DVL function: the inhibition of DIX- and DEP-domain mediated polymerization and interaction of DVL PDZ domain with its ligands.
Identifiants
pubmed: 34382124
doi: 10.1007/164_2021_527
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Dishevelled Proteins
0
Phosphoproteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-135Informations de copyright
© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.
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