Dataset Information

ZNRF3 and RNF43 are active monomeric E3 ligases that self-associate

ABSTRACT: Crosslinking mass spectrometry was used to identify the site of dimerization in the RING domain of ZNRF3. The two proteins, ZNRF3 and RNF43 have a key role in regulating the number of Frizzled (FZD) receptor on cells and their inactivation causes cancer. This is because they are RING E3 ligases that promote the ubiquitylation and internalisation of FZD, thereby turning off WNT signalling. Here we identify the key determinants of ubiquitin transfer by ZNRF3 and RNF43 and report the structure of the RING domain from ZNRF3. Our data indicate that the RING domain is monomeric, and that RING dimerization is not required for its ubiquitin ligase activity. However, the ectodomain of ZNRF3 forms dimers and our data supports a model where the cytoplasmic domains self-associate in cells even though RING dimerization is not required for activity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Torsten Kleffmann

LAB HEAD: Professor Catherine Day

PROVIDER: PXD070424 | Pride | 2026-07-30

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20080_L8B1_crosslink_1.RAW	Raw
	20080_L8B1_crosslink_1.msf	Msf
	20080_L8B1_crosslink_1.mzML	Mzml
	20080_L8B1_crosslink_centroid.mzML	Mzml
	20080_L8B1_deadxlink_2.msf	Msf

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Publications

ZNRF3 and RNF43 are active monomeric E3 ubiquitin ligases that self-associate.

Padala Prasanth P Rossig Claudia C Crowther Jennifer M JM Dobson Renwick C J RCJ Patel Monica M Kumar Abhishek A Kleffmann Torsten T Middleton Adam J AJ Day Catherine L CL

Science signaling 20260630 944

The WNT signaling pathway regulates cell proliferation and stem cell maintenance. Its sustained and inappropriate activation results in excessive cell division and cancer. WNT signaling is activated upon interaction of the soluble WNT ligand with the Frizzled (FZD) receptor. The RING E3 ubiquitin ligases RNF43 and ZNRF3 promote the ubiquitylation and internalization of FZD, thereby turning off WNT signaling, and their inactivation causes cancer. Here, we identified the determinants of ubiquitin ...[more]

PMID: 42378331

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