Epigenetic Modification and a Role for the E3 Ligase RNF40 in Cancer Development and Metastasis
Overview
Authors
Affiliations
RNF40 (OMIM: 607700) is a really interesting new gene (RING) finger E3 ubiquitin ligase containing multiple coiled-coil domains and a C-terminal RING finger motif, which engage in protein-DNA and protein-protein interactions. RNF40 encodes a polypeptide of 1001 amino acids with a predicted molecular mass of 113,678 Da. RNF40 and its paralog RNF20 form a stable heterodimer complex that can monoubiquitylate histone H2B at lysine 120 as well as other nonhistone proteins. Cancer is a major public health problem and the second leading cause of death. Through its protein ubiquitylation activity, RNF40 acts as a tumor suppressor or oncogene to play major epigenetic roles in cancer development, progression, and metastasis, highlighting the essential function of RNF40 and the importance of studying it. In this review, we summarize current knowledge about RNF40 gene structure and the role of RNF40 in histone H2B monoubiquitylation, DNA damage repair, apoptosis, cancer development, and metastasis. We also underscore challenges in applying this information to cancer prognosis and prevention and highlight the urgent need for additional investigations of RNF40 as a potential target for cancer therapeutics.
Cheng J, Song B, Wei C, Zhang L, Liu X, Yang L J Cancer. 2025; 16(4):1281-1295.
PMID: 39895796 PMC: 11786033. DOI: 10.7150/jca.101911.
Kou C, Zhao X, Fan X, Sun R, Wang W, Qi M CNS Neurosci Ther. 2025; 31(1):e70210.
PMID: 39777866 PMC: 11707429. DOI: 10.1111/cns.70210.
LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism.
Liu Z, Fan K, Abudukeremu A, Gao M, Tan X, Mao X Cell Death Discov. 2024; 10(1):298.
PMID: 38909032 PMC: 11193757. DOI: 10.1038/s41420-024-02072-6.
Ancient eukaryotic protein interactions illuminate modern genetic traits and disorders.
Cox R, Papoulas O, Shril S, Lee C, Gardner T, Battenhouse A bioRxiv. 2024; .
PMID: 38853926 PMC: 11160598. DOI: 10.1101/2024.05.26.595818.
Protein degradation of Lsd1 is mediated by Bre1 yet opposed by during fly follicle development.
Lin C, Ting R, Ou Y, Shao T, Lee M iScience. 2024; 27(5):109683.
PMID: 38655201 PMC: 11035368. DOI: 10.1016/j.isci.2024.109683.