RNF43 explained

Ring finger protein 43 is a protein that in humans is encoded by the RNF43 gene.^[1]

Function

The protein encoded by this gene is a RING-type E3 ubiquitin ligase and is predicted to contain a transmembrane domain, a protease-associated domain, an ectodomain, and a cytoplasmic RING domain. This protein is thought to negatively regulate Wnt signaling, and expression of this gene results in an increase in ubiquitination of frizzled receptors, an alteration in their subcellular distribution, resulting in reduced surface levels of these receptors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]. A nuclear function for the protein has also been proposed but recently it was shown that this is an artifact, nuclear staining being an artifact of the antibodies employed.^[2] Cancer-associated RNF43 mutations lead to activation of β-catenin signaling through aberrantly increasing Wnt-receptor levels at the membrane. Importantly, inactivating N-terminal RNF43 mutations render cancer cells sensitive to Wnt antagonists, but mutations elsewhere do not.^[3]

Further reading

• Yagyu R, Furukawa Y, Lin YM, Shimokawa T, Yamamura T, Nakamura Y . A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer . Int. J. Oncol. . 25 . 5 . 1343–8 . November 2004 . 15492824 .
• Sugiura T, Yamaguchi A, Miyamoto K . A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95 . Exp. Cell Res. . 314 . 7 . 1519–28 . April 2008 . 18313049 . 10.1016/j.yexcr.2008.01.013 .
• Shinada K, Tsukiyama T, Sho T, Okumura F, Asaka M, Hatakeyama S . RNF43 interacts with NEDL1 and regulates p53-mediated transcription . Biochem. Biophys. Res. Commun. . 404 . 1 . 143–7 . January 2011 . 21108931 . 10.1016/j.bbrc.2010.11.082 . 2115/44929 . free .
• Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJ, Maurice MM, Clevers H . Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors . Nature . 488 . 7413 . 665–9 . August 2012 . 22895187 . 10.1038/nature11308 . 2012Natur.488..665K . 4386072 .
• Ryland GL, Hunter SM, Doyle MA, Rowley SM, Christie M, Allan PE, Bowtell DD, Gorringe KL, Campbell IG . RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary . J. Pathol. . 229 . 3 . 469–76 . February 2013 . 23096461 . 10.1002/path.4134 . 24919944 . free .
• Xing C, Zhou W, Ding S, Xie H, Zhang W, Yang Z, Wei B, Chen K, Su R, Cheng J, Zheng S, Zhou L . Reversing effect of ring finger protein 43 inhibition on malignant phenotypes of human hepatocellular carcinoma . Mol. Cancer Ther. . 12 . 1 . 94–103 . January 2013 . 23136185 . 10.1158/1535-7163.MCT-12-0672 . free .
• Jiang X, Hao HX, Growney JD, Woolfenden S, Bottiglio C, Ng N, Lu B, Hsieh MH, Bagdasarian L, Meyer R, Smith TR, Avello M, Charlat O, Xie Y, Porter JA, Pan S, Liu J, McLaughlin ME, Cong F . Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma . Proc. Natl. Acad. Sci. U.S.A. . 110 . 31 . 12649–54 . July 2013 . 23847203 . 3732970 . 10.1073/pnas.1307218110 . 2013PNAS..11012649J . free .
• Zou Y, Wang F, Liu FY, Huang MZ, Li W, Yuan XQ, Huang OP, He M . RNF43 mutations are recurrent in Chinese patients with mucinous ovarian carcinoma but absent in other subtypes of ovarian cancer . Gene . 531 . 1 . 112–6 . November 2013 . 24001777 . 10.1016/j.gene.2013.08.054 .
• Zebisch M, Xu Y, Krastev C, MacDonald BT, Chen M, Gilbert RJ, He X, Jones EY . Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin . Nat Commun . 4 . 2787 . 2013 . 24225776 . 3905715 . 10.1038/ncomms3787 . 2013NatCo...4.2787Z .

Notes and References

1. Web site: Entrez Gene: Ring finger protein 43. 2018-02-21.
2. Li S, Zhang R, Lavrijsen M, van den Bosch TP, Peppelenbosch MP, Smits R . Issues with RNF43 antibodies to reliably detect intracellular location. . PLOS ONE . 18 . 4. e0283894 . 2023. 37023034 . 10.1371/journal.pone.0283894 . free. 10079101 . 2023PLoSO..1883894L .
3. Li S, Lavrijsen M, Bakker A, Magierowski M, Magierowska K, Liu P, Wang W, Peppelenbosch MP, Smits R . Commonly observed RNF43 mutations retain functionality in attenuating Wnt/β-catenin signaling and unlikely confer Wnt-dependency onto colorectal cancers . Oncogene . 39 . 17. 3458–3472 . 2020. 32103169 . 10.1038/s41388-020-1232-5 .