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Croatian medical journal, Vol.55 No.5 October 2014. -

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.



Autor: Anja Kafka - ; Laboratory of Neuro-oncology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagr

Fuente: http://hrcak.srce.hr/



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