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@inbook{1823457,
author = {Micka, Miroslav and Bryja, Vítězslav},
address = {Cham (Švýcarsko)},
booktitle = {Pharmacology of the WNT Signaling System},
doi = {http://dx.doi.org/10.1007/164_2021_527},
editor = {Schulte G., Kozielewicz P.},
keywords = {Casein kinase 1; Dishevelled; DIX oligomerization; PDZ inhibitors; Wnt signalling-related diseases},
howpublished = {tištěná verze "print"},
language = {eng},
location = {Cham (Švýcarsko)},
isbn = {978-3-030-85498-0},
pages = {117-135},
publisher = {Springer},
title = {Can We Pharmacologically Target Dishevelled: The Key Signal Transducer in the Wnt Pathways?},
url = {https://link.springer.com/chapter/10.1007/164_2021_527},
year = {2021}
}
TY - CHAP
ID - 1823457
AU - Micka, Miroslav - Bryja, Vítězslav
PY - 2021
TI - Can We Pharmacologically Target Dishevelled: The Key Signal Transducer in the Wnt Pathways?
VL - Handbook of Experimental Pharmacology, vol. 269
PB - Springer
CY - Cham (Švýcarsko)
SN - 9783030854980
KW - Casein kinase 1
KW - Dishevelled
KW - DIX oligomerization
KW - PDZ inhibitors
KW - Wnt signalling-related diseases
UR - https://link.springer.com/chapter/10.1007/164_2021_527
N2 - 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.
ER -
MICKA, Miroslav and Vítězslav BRYJA. Can We Pharmacologically Target Dishevelled: The Key Signal Transducer in the Wnt Pathways? In Schulte G., Kozielewicz P. \textit{Pharmacology of the WNT Signaling System}. Cham (Švýcarsko): Springer, 2021, p.~117-135. Handbook of Experimental Pharmacology, vol. 269. ISBN~978-3-030-85498-0. Available from: https://dx.doi.org/10.1007/164\_{}2021\_{}527.
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