Skip to Content
MilliporeSigma

USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification.

Cell reports (2019-07-25)
Casey P Nielsen, Kristin K Jernigan, Nicole L Diggins, Donna J Webb, Jason A MacGurn
ABSTRACT

The WNT signaling network is comprised of multiple receptors that relay various input signals via distinct transduction pathways to execute multiple complex and context-specific output processes. Integrity of the WNT signaling network relies on proper specification between canonical and noncanonical pathways, which presents a regulatory challenge given that several signal transducing elements are shared between pathways. Here, we report that USP9X, a deubiquitylase, and WWP1, an E3 ubiquitin ligase, regulate a ubiquitin rheostat on DVL2, a WNT signaling protein. Our findings indicate that USP9X-mediated deubiquitylation of DVL2 is required for canonical WNT activation, while increased DVL2 ubiquitylation is associated with localization to actin-rich projections and activation of the planar cell polarity (PCP) pathway. We propose that a WWP1-USP9X axis regulates a ubiquitin rheostat on DVL2 that specifies its participation in either canonical WNT or WNT-PCP pathways. These findings have important implications for therapeutic targeting of USP9X in human cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Rho (-A Antibody, -B, -C), clone 55, clone 55, Upstate®, from mouse
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Sigma-Aldrich
Anti-VANGL1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Rho Activation Assay Kit, PP1/PP2A Toolbox for the selective in vitro dephosphorylation of proteins.
Sigma-Aldrich
1,10-Phenanthroline monohydrate, reagent grade