Ask about this productRelated genes to: RNF40 Blocking Peptide
- Gene:
- RNF40 NIH gene
- Name:
- ring finger protein 40
- Previous symbol:
- -
- Synonyms:
- KIAA0661, RBP95, BRE1B, STARING
- Chromosome:
- 16p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-15
- Date modifiied:
- 2017-12-06
Related products to: RNF40 Blocking Peptide
Related articles to: RNF40 Blocking Peptide
- The ubiquitin‑proteasome system, a key protein degradation machinery in humans, mediates substrate recognition and proteolysis through ubiquitin‑tagged targeting of macromolecular proteins to the 26S proteasome. This evolutionarily conserved system orchestrates fundamental cell processes, including cell cycle progression, DNA damage repair, immune regulation, signal transduction and clearance of misfolded proteins. Its functional integrity is involved in the pathogenesis of various malignancies (breast and small cell lung cancer and colorectal adenocarcinoma) and degenerative diseases (Parkinson's disease). As a really interesting new gene‑type E3 ubiquitin ligase, ring finger protein (RNF)40 has emerged as a key regulator of both physiological homeostasis and disease progression. The present review systematically examines RNF40 structural architecture and its multifaceted roles in ubiquitination‑dependent proteostasis, epigenetic modulation and DNA repair mechanisms, as well as its tumor‑specific regulatory networks across cancer subtypes and therapeutic potential as a novel drug target. - Source: PubMed
Publication date: 2026/04/30
Wu ZikunYang HangChen GuanglongZhao WeijieBao BangheLuv ChaiZhu WenpuLiu FaqiangAi HuihanLi Zhi - Centrosomes must undergo maturation in the G2/M phases to activate the microtubule-organizing activity, ensuring proper bipolar spindle assembly and chromosome segregation. Polo-like kinase 1(PLK1) is crucial for centrosome maturation. How the cell cycle controls timely PLK1 recruitment and centrosome maturation remains elusive. Here, we find that the ubiquitin E3 ligase RNF40 localizes to centrosomes and is phosphorylated by CDK1 on T529/T557 in the G2/M phases. This phosphorylation primes its binding to PLK1 and promotes timely PLK1 recruitment and centrosome maturation, establishing the CDK1-RNF40-PLK1 cascade as a mechanism controlling centrosome maturation. We also find that RNF40 is acetylated in interphase and undergoes an acetylation-to-phosphorylation transition in late G2 and M phases, which permits timely activation of the CDK1-RNF40-PLK1 cascade. Constitutive RNF40 acetylation or deficient RNF40 phosphorylation impairs PLK1 localization, microtubule nucleation, and bipolar spindle assembly, causing mitotic catastrophe. Thus, the cell cycle-dependent transition of RNF40 modifications ensures timely centrosome maturation and chromosome segregation. - Source: PubMed
Publication date: 2026/03/20
Li JiminLiang JianqiangChen GuifangWang XuejieWang YanyanZhan JingfeiGuo YunjingWang JiadongChen Xuefeng - Lysine demethylase 6A (KDM6A) is a critical epigenetic regulator implicated in development, cancer, and viral infection. Although KDM6A enhances coronavirus entry by modulating viral receptor expression, the mechanisms governing its protein stability remain unknown. Here, we show that ubiquitin-specific protease 7 (USP7) promotes diverse coronavirus infection, including SARS-CoV, SARS-CoV-2, MERS-CoV, and MHV, and represents a broad-spectrum anti-coronavirus target. Genetic and pharmacological inhibition of USP7 attenuates the expression of coronavirus receptors ACE2, DPP4, and Ceacam1, thereby impeding viral entry. Mechanistically, USP7 deubiquitinates KDM6A by removing K48-linked polyubiquitin chains to prevent its proteasomal degradation. Conversely, the E3 ubiquitin ligase RNF40 catalyzes K6- and K11-linked ubiquitination of KDM6A, which serves as a signal for recognition by TAX1BP1 for autophagic degradation, to restrict diverse coronavirus infection. Pharmacological inhibition of USP7 with FT671 and XL177A reduces KDM6A stability and viral receptor expression, and confers resistance to MERS-CoV, SARS-CoV, and all major SARS-CoV-2 variants of concern, including those resistant to remdesivir in primary human airway and intestinal epithelial cells. In mice, FT671 treatment was well tolerated, reduced Ceacam1 expression, and protected against MHV-A59 infection. Collectively, our findings unveil an antagonistic ubiquitin-mediated regulatory circuit that controls KDM6A stability, viral receptor levels, and coronavirus infection. - Source: PubMed
Publication date: 2026/02/15
Huang Meng-ZhuoYang Zhong-YuanWang ShiGe YanLin LanAlfajaro Mia MadelFiller Renata BSong Wan-YaoKong Ming-ZhuWei Jin - The mono-ubiquitination of the histone protein H2B (H2BUb1) has important functions in transcription, DNA repair, and other chromatin-related processes. The reaction is catalyzed by Bre1 and the homologous RNF20/RNF40 complex in the budding yeast and human cells, respectively, and is promoted by their respective interaction partners, Lge1 and WAC. The mechanism of the Bre1-Lge1 and RNF20/RNF40-WAC interactions is poorly understood. Here, we present the crystal structure of the Bre1-Lge1 complex and an AlphaFold predicted structure model of the RNF20/RNF40 complex bound with WAC, as well as in vitro and in vivo experiments to assess the interaction mechanism and function. Our study revealed extensive Bre1-Lge1 and RNF20/RNF40-WAC interfaces and a structural homology shared by these interfaces, but completely different sets of key electrostatic interactions at these interfaces that are crucial for the binding and encode the binding specificity. We further found that these interactions play critical roles in the Bre1-catalyzed H2BUb1 reaction and processes it regulates. Our data provide insights into the mechanism of the Bre1-Lge1 and RNF20/RNF40-WAC interactions. - Source: PubMed
Shi MengWang XuejieZhang HangWen YajiaoLiu QianqianChen PuChen XuefengXiang Song - The activation of H2B K120 monoubiquitylation (H2BK120ub) by H2B S112 GlcNAcylation (H2BS112GlcNAc) has an important role in regulating transcriptional activation, yet its mechanism remains unclear. Here we chemically synthesized H2BS112GlcNAc-modified nucleosomes and quantitatively evaluated how H2BS112GlcNAc stimulates ubiquitylation by RNF20/RNF40-RAD6A E3-E2 enzymes. Cryo-electron microscopy determination of a chemically trapped RNF20/RNF40-RAD6A-Ub-H2BS112GlcNAc nucleosome complex revealed that the H2BS112GlcNAc moiety interacts with the E2 enzyme RAD6A but not the E3 ligase RNF20/RNF40. Mutagenesis and kinetics analyses demonstrated that H2BS112GlcNAc allosterically stimulates ubiquitin transfer from the RAD6A~Ub thioester to H2B K120 by enhancing the nucleophilicity of H2B K120. Structure‒activity relationship analysis further identified the essential roles of the C2 N-acetyl group and the β-configuration of C1 on the H2BS112GlcNAc moiety. These findings provide the structural evidence of histone posttranslational modification crosstalk involving O-GlcNAcylation and reveal how O-GlcNAcylation can allosterically stimulate enzyme activity through substrate modification. - Source: PubMed
Publication date: 2026/01/06
Deng ZhihengTao ShixianDu YunxiangLi YuleiZhang LiyingShi QiangDu XiaoruSun MaoshenTong ZebinPan ManLiu LeiAi Huasong