Ask about this productRelated genes to: UBE2K antibody
- Gene:
- UBE2K NIH gene
- Name:
- ubiquitin conjugating enzyme E2 K
- Previous symbol:
- HIP2
- Synonyms:
- HYPG, UBC1
- Chromosome:
- 4p14
- Locus Type:
- gene with protein product
- Date approved:
- 1997-08-28
- Date modifiied:
- 2016-03-14
Related products to: UBE2K antibody
Related articles to: UBE2K antibody
- Aberrant alternative polyadenylation (APA) and alternative splicing (AS) contribute to numerous diseases, including cancer; however, their coordinated roles in ovarian cancer remain poorly understood. Here, we investigated CPSF7, an APA factor markedly upregulated in ovarian cancer and associated with poor prognosis. Silencing CPSF7 suppressed proliferation, migration, and invasion of ovarian cancer cells, while antisense oligonucleotides (ASOs) targeting CPSF7 reduced tumor growth in a patient‑derived xenograft (PDX) model. Mechanistically, knockdown of the splicing factor SNRPD2 induced exon 4 skipping in CPSF7 pre‑mRNA. Loss of exon 4 disrupted the RNA recognition motif (RRM) domain essential for CPSF7‑mediated pre‑mRNA cleavage and polyadenylation, and introduced premature termination codons (PTCs) that generated noncoding transcripts subject to nonsense‑mediated decay (NMD), thereby reducing CPSF7 expression. Thus, efficient splicing mediated by SNRPD2 is crucial for sustaining high CPSF7 levels in ovarian cancer cells. Functional assays showed that CPSF7 knockdown reduced proliferation and metastatic potential in cells with elevated SNRPD2, suggesting that CPSF7 is a key mediator of SNRPD2-driven oncogenesis. Moreover, CPSF7 governed specific APA events to maintain transcript stability, with UBE2K identified as a critical downstream target. CPSF7 preferentially bound distal polyadenylation signals (PASs) within the predominant UBE2K transcript (UBE2K-201), thereby increasing its mRNA stability and maintaining high functional UBE2K expression. Collectively, these findings reveal that AS and APA are interconnected in ovarian cancer via the SNRPD2-CPSF7-UBE2K axis, which drives disease progression and represents a promising target for therapeutic intervention. - Source: PubMed
Publication date: 2026/05/07
Li YingweiChen ZhongshaoDiao YuchaoGao QianqianGao YuehanPu YingyingYang Ning - Breast cancer (BC) remains one of the major threats to women's health in the 21st century, due to its high incidence and mortality rates. Ubiquitin-conjugating enzymes, as members of the ubiquitin-proteasome system, are responsible for numerous cellular physiological processes. However, ubiquitin-conjugating enzymes may also play unexpected roles in other physiological activities, such as phosphorylation, lactylation, and even methylation. The physiological function of the ubiquitin-conjugating E2 enzyme UBE2K in BC remains unknown. As a result, we looked into UBE2K's physiological role in the malignant development of BC. - Source: PubMed
Publication date: 2025/12/21
Mou JianchengTang HongchaoHu XiaogeYang ZhuotaoSu HaotianQian DaLi ChenhongLiu HaotianYe ZhihaoXu MingxingLiu ShuyanZheng QinghuiLiu XiaozhenZeng XinXu QiuranMeng Xuli - The heterotrimeric complex serine-threonine protein phosphatase 2 A (PP2A) is integral to the regulation of essential cellular processes. It is particularly crucial in spermatogenesis, where it is indispensable for meiosis, mitosis, sperm capacitation, and apoptosis. Previous research has concentrated on the knockdown of the catalytic subunit of PP2A, PPP2CA, in germ cells using Ddx4-Cre, resulting in male mouse sterility, disrupted meiotic recombination, and meiotic arrest of spermatocytes. To further elucidate the role of PP2A in spermatogenesis, we performed transcriptomic and proteomic sequencing analyses on the testes of knockout and control mice. A nine-quadrant map was developed to depict the differential expression of genes and proteins. Our analyses identified 1732 differentially expressed genes, which exhibited a strong positive correlation with the trends in differential protein expression. Gene Ontology (GO) enrichment analysis indicated a significant downregulation of genes involved in spermatogenesis, sperm cell development, and sperm cell differentiation. Furthermore, KEGG enrichment analysis revealed a notable enrichment of differentially expressed genes within the ubiquitin-mediated proteolysis pathway. In knockout mouse testicular tissue, testicular expression of the ubiquitin-related gene, UBE2K, was markedly downregulated, which was associated with the accumulation of histone H3, upregulation of the methyltransferase SETDB1, and increased levels of H3K9me3. Similarly, knockdown of Ppp2ca in GC2 cells resulted in decreased UBE2K expression, histone H3 accumulation, SETDB1 upregulation, and elevated H3K9me3 levels, consistent with mirroring the phenotype observed in the knockout mice. Notably, the ubiquitin-related gene UBE2K was identified as a significant outlier in the nine-quadrant map, and real-time quantitative PCR confirmed that UBE2K transcript levels were significantly reduced in knockout mice compared to wild-type controls. These findings suggest that PP2A may regulate histon. - Source: PubMed
Publication date: 2025/11/25
Ju HuameiGeng ZiliangChen BinyanShang YuweiChen XiaWang DanniWang WenbinSun HuitingShi YichaoYu Jiajun - Intracellular pathogens frequently subjugate the ubiquitin system to evade host immune defenses and establish intracellular replication niches. Microsporidia are obligate intracellular animal parasites that typically cause self-limiting infections in humans, but can sometimes cause fatal disseminated disease. At present, the ubiquitin system of microsporidia is virtually unexplored. Here, we discover a likely effector deubiquitinase (DUB) of the otubain subgroup from the human pathogenic microsporidian , which we designate ehOTUB1. We find that ehOTUB1 selectively binds the human ubiquitin conjugating (E2) enzyme UBE2K and inhibits its ubiquitin conjugation activity independent of ehOTUB1 DUB activity. We show that ehOTUB1 obstructs docking of UBE2K onto ubiquitin E1 enzyme via steric conflict with ubiquitin in the E1 adenylation site to prevent ubiquitin transfer to UBE2K. This unconventional mechanism of E2 inhibition expands the known repertoire by which pathogens manipulate ubiquitin signaling, and suggests that direct inhibition of E2 enzymes may be a broader function of otubain subfamily DUBs than originally appreciated. - Source: PubMed
Publication date: 2025/08/01
Lawal TomiwaChang Alana HCarnley Lauren GCeloge Nehry YBlount Taylor AVied CynthiaNemec Antonia ATomko Robert J - Chemical trapping strategies have recently emerged as powerful approaches for investigating the structural dynamics of E3 ligase-catalyzed substrate ubiquitination. However, current ubiquitination-derived probes are limited to studying substrate mono- or diubiquitination events. Probes capable of investigating how E3 ligases accommodate E2-Ub conjugates and ubiquitinated substrates to generate longer ubiquitin chains remain unexplored. In this work, we report the development of two Cullin1 E3 ligase (CRL1)-dependent probes, Extension Probe and Extension Probe, which mimic transient intermediates formed during CRL1-catalyzed K48-linked diubiquitin and tetraubiquitin chain formation on substrate p27. Notably, a chemoenzymatic semisynthetic strategy was devised to generate Extension Probe, involving the enzymatic conjugation of a preformed K48-linked diubiquitin to a synthetic Ub-p27-degron construct using the E2 conjugating enzyme UBE2K. Both Extension Probe and Extension Probe formed stable complexes with N8-CRL1 (comprising neddylated Cullin1-Rbx1 and the substrate receptor complex Skp1-Skp2-Cks1), facilitating structural analysis by chemical cross-linking mass spectrometry (CX-MS) and cryo-electron microscopy (cryo-EM). Our results indicate the presence of multiple distinct conformations of the catalytic module (comprising the RING domain of Rbx1, CDC34-Ub, and the acceptor ubiquitin) within the di- and tetraubiquitination complexes, while the conformation of the Cullin1-Skp1-Skp2-Cks1 subunit remains unchanged. In conclusion, this work expands the toolkit available for chemical trapping strategies and provides advanced insights into CRL-catalyzed substrate polyubiquitination. - Source: PubMed
Publication date: 2025/06/25
Li ChuntongZhao FangyuZuo ChongZhang LiyingJing YangwodeLi XuChu Guo-ChaoShi LuyuZhang YingyueWang HanSun ShuzheSun MaoshenAi HuasongLiang Lu-JunLi Jinghong