UBE2O

Last update 08 May 2025

Basic Info

Synonyms

(E3-independent) E2 ubiquitin-conjugating enzyme, E2-230K, E2/E3 hybrid ubiquitin-protein ligase UBE2O

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Introduction

E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853).

100 Clinical Results associated with UBE2O

100 Translational Medicine associated with UBE2O

0 Patents (Medical) associated with UBE2O

Literatures (Medical) associated with UBE2O

01 Apr 2025·Cancer Letters

RSK2-mediated phosphorylation and degradation of UBE2O inhibits hepatocellular carcinoma growth and resistance to radiotherapy

Article

Author: Huang, Yumei ; Yang, Liu ; Meng, Yimei ; Lin, Ming ; Qiu, Anchen ; Xu, Yunhong

Radioresistance poses the main challenge in radiation therapy (RT) for liver cancer, with the DNA Damage response (DDR) being a crucial component of this resistance. Ubiquitin-conjugating enzyme E2O (UBE2O) has been implicated in regulating tumor proliferation, cholesterol metabolism, and drug resistance. However, the role of the ubiquitin-conjugating enzyme E2O (UBE2O) in DDR of liver cancer remains to be fully explored. We discovered an elevated expression of UBE2O within liver cancer tissues, which was notably associated with unfavorable prognoses in hepatocellular carcinoma (HCC) patients. Furthermore, we found that the suppression of UBE2O can effectively reduce the growth and resistance to radiotherapy of HCC cells in vitro and in vivo. Moreover, p90 ribosomal S6 kinase2 (RSK2) was confirmed as a novel interacting kinase of UBE2O, which mediated the phosphorylation and degradation of UBE2O at the Thr838 site. RSK2 inhibition promotes tumor proliferation and resistance to radiotherapy of HCC cells in vitro and in vivo, and these effects are abrogated upon UBE2O knockdown. Collectively, our work revealed that UBE2O promotes tumor progression and resistance to radiotherapy, which was negatively regulated by RSK2 for phosphorylation and degradation, indicating that the RSK2/UBE2O axis provides a potential radiosensitization target for HCC patients.

01 Feb 2025·Structure

Structural insights into the biochemical mechanism of the E2/E3 hybrid enzyme UBE2O

Article

Author: Chang, Qing ; Li, Wenqi ; Zhu, Wenning ; Zhou, Huan ; Cao, Dan ; Li, Long ; Zhang, Wei ; Huang, Hao ; Ye, Yuxin ; Niu, Xiaogang ; Xiong, Yuxian ; Fu, Ziyang ; Huang, Bin

The E2/E3 hybrid enzyme UBE2O plays important roles in key biological events, but its autoubiquitination mechanism remains largely unclear. In this study, we determined the crystal structures of full-length (FL) UBE2O from Trametes pubescens (tp) and its ubiquitin-conjugating (UBC) domain. The dimeric FL-tpUBE2O structure revealed interdomain interactions between the conserved regions (CR1-CR2) and UBC. The dimeric intermolecular and canonical ubiquitin/UBC interactions are mechanistically important for UBE2O functions in catalyzing the formation of free polyubiquitin chains and substrate ubiquitination. Beyond dimerization, autoubiquitination within the CR1-CR2 domain also regulates tpUBE2O activity. Additionally, we show that tpUBE2O catalyzes the formation of all seven types of polyubiquitin chains in vitro. The CR1-CR2/UBC and canonical ubiquitin/UBC interactions are important for the polyubiquitination of AMP-activated protein kinase α2 (AMPKα2) by human UBE2O (hUBE2O), which leads to tumorigenesis. These structural insights lay the groundwork for understanding UBE2O's mechanisms and developing structure-based therapeutics targeting UBE2O.

01 Dec 2024·Comparative Biochemistry and Physiology Part D: Genomics and Proteomics

Multi-organ transcriptomics analysis of a slowly growing fish rock carp (Procypris rabaudi) reveals insights into mechanism of growth rate regulation

Article

Author: Luo, Hui ; Su, Shengqi ; Ling, Jingning ; He, Wenping ; Wang, Anxiang ; Li, Yixiao ; Lv, Hongsen ; He, Yuanfa ; Yao, Weizhi ; Ye, Hua

To explore the patterns of differentially expressed genes (DEGs) associated with different growth rates in rock carp (Procypris rabaudi), transcriptome sequencing was performed on the muscle, liver, and brain tissues of rock carp. Subsequently, bioinformatics analysis was conducted, and 2129, 1380, and 415 DEGs were identified in the muscle, liver, and brain tissues, respectively. GO enrichment and KEGG pathway analysis revealed that genes related to appetite regulation, protein degradation and digestion, lipid transport and metabolisms, and glycolysis/gluconeogenesis were upregulated in individuals with slower growth rates. Differential expression analysis identified 21 genes associated with feeding and metabolism across three tissues, including mc4r, npy, and npry in brain tissue; fatp, fabp, pparα, and apo in liver tissue; and prss, ctrl, and cela in muscle tissue. All these genes were upregulated in the slow-growing fish. Furthermore, weighted gene co-expression network analyses, including three modules (yellow, turquoise, and brown), significantly associated with growth. A network map that included these three modules enabled the identification of a series of hub genes, including rp13a, ube2o, h6pd, etc. These genes may be key candidate genes regulating the growth of rock carp. This study contributes to a deeper understanding of the growth control mechanism in rock carp and offers a scientific basis for efficient breeding and species improvement.

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UBE2O

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