ZNRF3,RNF43 binds the FZD:LRP5/6 receptor complex

Stable Identifier
Homo sapiens
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ZNFR3 and RNF43 are plasma membrane E3 RING domain ubiquitin ligases that have been shown to ubiquitinate FZD proteins to promote their downregulation (Hao et al, 2012). Inhibition of ZNRF3 or RNF43 increases the protein level of FZD and LRP6 at the plasma membrane, and stably expressed ZNRF3 can be co-immunoprecipitated with endogenous LRP6 and FZD6 (Hao et al, 2012; Jiang et al 2013). Turnover of the LRP6 and FZD receptors appears to be regulated by multiubiquitination and is abrogated upon treatment with lysosomal inhibitors (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
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