Huwe1-mediated ubiquitylation of dishevelled defines a negative feedback loop in the Wnt signaling pathway.
Huwe1-mediated ubiquitylation of dishevelled defines a negative feedback loop in the Wnt signaling pathway.
Data from ProteomeXchange, PXD ID: PXD000781. File: KN_Ubi_endo_130528_minus_fr_65min_01.mzml. Published as part of Sci Signal. 2014 Mar 18;7(317):ra26 . From the Abstract: {{i}} In human embryonic kidney 293T cells, knockdown of the EEL-1 homolog Huwe1 enhanced the activity of a Wnt reporter in cells stimulated with Wnt3a or in cells that overexpressed casein kinase 1 (CK1) or a constitutively active mutant of the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6). However, knockdown of Huwe1 had no effect on reporter gene expression in cells expressing constitutively active beta-catenin, suggesting that Huwe1 inhibited Wnt signaling upstream of beta-catenin and downstream of CK1 and LRP6. Huwe1 bound to and ubiquitylated the cytoplasmic Wnt pathway component Dishevelled (Dvl) in a Wnt3a- and CK1ε-dependent manner. Mass spectrometric analysis showed that Huwe1 promoted K63-linked, but not K48-linked, polyubiquitination of Dvl. {{/i}} Note: the ProteomeXchange entry indicates that these data files correspond to mouse cell-derived samples, however they are all from human HEK-293 cells.
Proteomics
Proteomics
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