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Regulation of FZD by ubiquitination

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-4641263

PubChem

R-HSA-4641263

Description

WNT responsiveness is influenced by expression levels of FZD and LRP proteins. Levels of these receptors at the cell surface are regulated in part by endocytosis, but the mechanisms are not fully elucidated (Garliardi et al, 2008). A number of recent studies have identified a role for ubiquitination in the localization and turnover of WNT receptors at the plasma membrane. ZNRF3 and RNF43 are E3 ligases that have been shown to ubiquitinate FZD proteins and promote their lysosomal degradation, while the deubiquitinating enzyme USP8 promotes recycling of the receptor back to the plasma membrane (Hao et al, 2012; Mukai et al, 2010). This balance of ubiquitination and deubiquitination is in turn regulated by the R-spondin (RSPO) proteins, agonists of WNT signaling which appear to act by downregulating ZNRF3 and RNF43, thus potentiating both canonical and non-canonical pathways (Hao et al, 2012; reviewed in Abo and Clevers, 2012; Fearon and Spence, 2012, Papartriantafyllou, 2012).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 18 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O60353	Frizzled-6	FZD6	view
O75197	Low-density lipoprotein receptor-related protein 5	LR3 LRP5 LRP7	view
O75473	Leucine-rich repeat-containing G-protein coupled receptor 5	GPR49 GPR67 LGR5	view
O75581	Low-density lipoprotein receptor-related protein 6	LRP6	view
P40818	Ubiquitin carboxyl-terminal hydrolase 8	KIAA0055 UBPY USP8	view
P56704	Protein Wnt-3a	WNT3A	view
P62979	Ubiquitin-ribosomal protein eS31 fusion protein	RPS27A UBA80 UBCEP1	view
P62987	Ubiquitin-ribosomal protein eL40 fusion protein	UBA52 UBCEP2	view
Q13467	Frizzled-5	C2orf31 FZD5	view
Q2I0M5	R-spondin-4	C20orf182 RSPO4	view

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