Original scientific paper
https://doi.org/10.3325/cmj.2014.55.459
The cellular story of dishevelleds
Anja Kafka
; Laboratory of Neuro-oncology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
Sandra Bašić-Kinda
; Division of Hematology University Hospital Center Zagreb and University of Zagreb School of Medicine, Croatia
Nives Pećina-Šlaus
orcid.org/0000-0002-3334-7671
; Division of Hematology University Hospital Center Zagreb and University of Zagreb School of Medicine, Croatia
Abstract
Dishevelled (DVL) proteins, three of which have been identified
in humans, are highly conserved components of canonical
and noncanonical Wnt signaling pathways. These
multifunctional proteins, originally discovered in the fruit
fly, through their different domains mediate complex signal
transduction: DIX (dishevelled, axin) and PDZ (postsynaptic
density 95, discs large, zonula occludens-1) domains
serve for canonical beta-catenin signaling, while PDZ
and DEP (dishevelled, Egl-10, pleckstrin) domains serve
for non-canonical signaling. In canonical or beta-catenin
signaling, DVL forms large molecular supercomplexes at
the plasma membrane consisting of Wnt-Fz-LRP5/6-DVLAXIN.
This promotes the disassembly of the beta-catenin
destruction machinery, beta-catenin accumulation, and
consequent activation of Wnt signaling. Therefore, DVLs
are considered to be key regulators that rescue cytoplasmic
beta-catenin from degradation. The potential medical
importance of DVLs is in both human degenerative
disease and cancer. The overexpression of DVL has been
shown to potentiate the activation of Wnt signaling and it
is now apparent that up-regulation of DVLs is involved in
several types of cancer.
Keywords
Hrčak ID:
129950
URI
Publication date:
15.10.2014.
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