ZNRF3 ubiquitinates FZD to promote its downregulation

Stable Identifier
Reaction [transition]
Homo sapiens
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ZNRF3 has been shown to ubiquitinate FZD4 in vivo, and inhibition of ZNRF3/RNF43 increases the protein levels of LRP6 and FZD8 at the cell surface (Hao et al, 2012; Jiang et al, 2013). Degradation of FZD and LRP is abrogated upon treatment of cells with bafilomycin A1 but not with MG132, suggesting that degradation of the receptors occurs in the lysosome. Consistent with this, mutational analysis suggests that FZD4 is multi-monoubiquitinated (Mukai et al, 2010).

Literature References
PubMed ID Title Journal Year
22575959 ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner

Mickanin, C, Zhang, Y, Bouwmeester, T, Zamponi, R, Xie, Y, Liu, D, Charlat, O, Kirschner, MW, Cong, F, Porter, JA, Avello, M, Lei, H, Serluca, FC, Finan, PM, Oster, E, Hao, HX, Ma, Q, Ruffner, H, Mao, X

Nature 2012
20495530 Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt

Watanabe, W, Goto, S, Komada, M, Awano, W, Yamamoto-Hino, M, Mukai, A

EMBO J. 2010
23847203 Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma

Lu, B, Liu, J, Woolfenden, S, Hsieh, MH, Smith, TR, Pan, S, Xie, Y, Bagdasarian, L, Charlat, O, Meyer, R, Ng, N, Bottiglio, C, McLaughlin, ME, Cong, F, Growney, JD, Jiang, X, Porter, JA, Avello, M, Hao, HX

Proc. Natl. Acad. Sci. U.S.A. 2013
Catalyst Activity

ubiquitin protein ligase activity of N4GlycoAsn-PalmS-WNT3A:FZD:LRP5/6:ZNRF3/RNF43 [plasma membrane]

Orthologous Events
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