Ask about this productRelated genes to: KIAA1333 antibody
- Gene:
- G2E3 NIH gene
- Name:
- G2/M-phase specific E3 ubiquitin protein ligase
- Previous symbol:
- KIAA1333
- Synonyms:
- FLJ20333, PHF7B
- Chromosome:
- 14q12
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-21
- Date modifiied:
- 2014-11-19
Related products to: KIAA1333 antibody
Related articles to: KIAA1333 antibody
- In the pathogenesis of hepatocellular carcinoma (HCC), impaired CD8 T cell function is a critical factor in immune evasion. Although CLCN2 has been implicated in immunomodulation, its role in regulating CD8 T cell-mediated antitumor immunity in HCC remains unclear. The expression of G2E3 in HCC was analyzed using the TCGA database, qPCR, and western blot. The UbiBrowser database was employed to predict CLCN2 as a downstream substrate of G2E3. Protein interactions were validated via Co-IP and in vivo ubiquitination assays. IFN-γ, TNF-α, and Granzyme B levels were measured using ELISA kits, while CD44 and CD134 levels in CD8 T cells were examined via flow cytometry. The cytotoxic activity of CD8 T cells against HCC cells was evaluated using an LDH assay. An allograft mouse tumor model was utilized to determine whether the G2E3-CLCN2 axis drove HCC progression by suppressing T cell immunity. We herein discovered that G2E3 was highly expressed in HCC and positively linked with poor prognosis. Mechanistically, G2E3 functioned as an E3 ubiquitin ligase, mediating the ubiquitination and subsequent degradation of CLCN2. Rescue experiments revealed that CLCN2 enhanced the antitumor activity of CD8 T cells, whereas G2E3 overexpression attenuated this effect. Furthermore, in an allograft mouse tumor model, activation of the G2E3-CLCN2 axis reduced CD8 T cell infiltration and activity in tumors, thereby driving tumor growth. This investigation elucidates the molecular mechanism by which HCC suppresses CD8 T cell function to facilitate immune escape, suggesting that targeting the G2E3-CLCN2 axis may represent a potential therapeutic strategy to enhance antitumor immunity. - Source: PubMed
Zhou FanChen TingTan XingguoYu JunXiao MengzhiGuo Jun - Compartmentalization of eukaryotic genome into euchromatin and heterochromatin is of critical biological significance. Previous studies have suggested a self-templating pathway involving the reading and writing of histone H3 lysine 9 methylation by SUV39H as the core mechanism for heterochromatin reassembly during cell division. In fission yeast, the mammalian SUV39H homologue Clr4 forms a complex containing ubiquitin ligase Cul4, which catalyses H3K14 mono-ubiquitination (H3K14ub) to promote heterochromatin formation. However, whether heterochromatin reassembly in dividing mammalian cells involves a similar pathway is unknown. Here we identified G2E3 as an H3K14ub-specific, pericentromeric heterochromatin-localized E3 ligase. G2E3-catalysed H3K14ub potentiates histone H3 lysine 9 trimethylation (H3K9me3) by SUV39H and is specifically required for SUV39H compartmentalization and H3K9me3 in pericentromeric heterochromatin. Mechanistically, we found that G2E3 is highly expressed in G2/M phase and associates with mitotic chromosomes in an RNA-dependent manner to catalyse H3K14ub, which is essential for the subsequent sequential recruitment of SUV39H and HP1. The SUV39H chromodomain is a reader of dual H3K9me3 and H3K14ub modifications and SUV39H associates with pericentromeric heterochromatin primarily through its H3K14ub-binding activity. Notably, loss of G2E3 severely impairs pericentromeric heterochromatin organization and results in the aberrant accumulation of SUV39H and H3K9me3 in numerous euchromatin regions and widespread transcriptional repression. Thus, our findings revealed the H3K14ub-dependent SUV39H compartmentalization as a unified mechanism of pericentromeric heterochromatin formation, which is essential for proper euchromatin compartmentalization and transcriptional regulation. - Source: PubMed
Publication date: 2025/10/15
Huang YuanyongSun YimeiQi HongyunJiang QuanlongLi JialunChang MingzhiLi XinyanShu LeiDuan XiaoyaWang YiqinFang KailunMao HaileiHan MengmengWeng YuanZhang QiaoChen ZhaosuWei WeiSong GaojieZhang QiansenLi JiwenHan Jing-Dong JChen Charlie DeguiWong Jiemin - Autophagy is a tightly regulated process essential for cellular homeostasis, with ubiquitination playing a crucial role in its regulation. However, the specific ubiquitin related factors involved in autophagic flux remain largely unexplored. Identifying these regulators is essential for advancing the mechanistic understanding of autophagy and its broader implications in cellular function. This study aimed to identify novel ubiquitination-associated regulators of autophagy. To achieve this, we conducted a CRISPR-Cas9 loss-of-function screen targeting 660 ubiquitination-related genes in pancreatic cancer cells expressing the mCherry-GFP-LC3 autophagy flux reporter system. Among the top candidates, we identified G2E3, a G2/M-phase-specific E3 ubiquitin ligase, as a previously unrecognized autophagy regulator. Subsequent functional analyses revealed that G2E3 knock out led to a significant accumulation of LC3B-II and GABARAPs, indicative of impaired autophagic flux. Further confocal imaging demonstrated that the co-localization of LC3B with LAMP1-positive lysosomes was significantly reduced in G2E3 knock out cells, suggesting defective autophagosome-lysosome fusion. Mechanistically, G2E3 directly interacts with GABARAP and GABARAPL1, but not LC3B, positioning it as a key regulator of late-stage autophagy. Additionally, G2E3 knock out cells exhibited reduction in migration and invasion capability, suggesting its role in cancer progression. These findings establish G2E3 as a novel ubiquitin-related regulator of autophagy, specifically facilitating autophagosome-lysosome fusion via a GABARAPs-dependent mechanism. This study reveals a previously unrecognized role of G2E3 in late-stage autophagy and suggests that targeting G2E3 could provide a potential therapeutic approach for modulating autophagy-dependent cellular processes, including cancer progression. - Source: PubMed
Publication date: 2025/10/09
Gong YumeiLeon MarcMo HuaqingPengpaeng PremkamolYang HaiLu YanxiYin ZhiqiangBenard AlanZhou YongGrützmann RobertPilarsky Christian - Despite the current diagnostic and therapeutic methods for colorectal cancer (CRC), patients are often diagnosed at advanced stages of colorectal cancer. Recently, numerous investigations have highlighted the role of lncRNAs in cancer development and progression. This study investigated less well-characterized genes in the colorectal cancer metastasis process. - Source: PubMed
Publication date: 2025/01/30
Kenari Shahrbanoo NandoustMohamadynejad ParisaMoghanibashi MehdiBagheri AbouzarRouhi Leila - Structural variants (SVs) such as deletions, duplications, and insertions are known to contribute to phenotypic variation but remain challenging to identify and genotype. A more complete, accessible, and assessable collection of SVs will assist efforts to study SV function in cattle and to incorporate SV genotyping into animal evaluation. - Source: PubMed
Publication date: 2024/09/30
Grant Jason RHerman Emily KBarlow Lael DMiglior FilippoSchenkel Flavio SBaes Christine FStothard Paul