Ask about this productRelated genes to: Dtx3 Blocking Peptide
- Gene:
- DTX3 NIH gene
- Name:
- deltex E3 ubiquitin ligase 3
- Previous symbol:
- -
- Synonyms:
- FLJ34766, RNF154
- Chromosome:
- 12q13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-23
- Date modifiied:
- 2016-10-05
Related products to: Dtx3 Blocking Peptide
Related articles to: Dtx3 Blocking Peptide
- Colorectal cancer (CRC) is one of the most common malignant tumors of digestive system. As ubiquitin E3 ligases, Deltex (DTX) family proteins have been reported to be associated with multiple cancers. However, the role of Deltex-3 (DTX3) in CRC cells remains unclear. The study aimed to investigate the role of DTX3 in CRC. - Source: PubMed
Publication date: 2025/09/26
Ma ZhennanGong XiuqingZhang Xiaowei - ADP-ribosylation can occur as mono-ADP-ribose (MAR) or be extended into poly-ADP-ribose (PAR). Tankyrase, a PAR transferase, adds PAR to itself and other proteins targeting them for proteasomal degradation via the PAR-binding E3 ligase RNF146. This degradation can be counteracted by RING-UIM E3 ligases RNF114 and RNF166, although the process is unclear. Here, we identify a mechanism that can regulate the balance between MAR and PAR on tankyrase to control degradation. We show that Deltex E3 ligases DTX2 and DTX3 catalyze monoubiquitylation of tankyrase in cells. This ubiquitylation occurs, not on a (canonical) lysine, but rather on MAR, creating a monoubiquitin-MAR hybrid mark. RNF114 and RNF166 recognize this mark using a unique hybrid reader domain and further diubiquitylate it. This ubiquitylation of MAR, which occurs near the ADP-ribose addition site, prevents PAR formation, antagonizing the action of the PAR-binding E3 ligase RNF146 and stabilizing tankyrase. These findings reveal an interplay between ubiquitin, ADP-ribose, and E3 ligases in cellular signaling. - Source: PubMed
Publication date: 2025/09/03
Perrard JeromeGao KevinRing KatherineSmith Susan - Infants born to mothers with obesity have increased risk for later development of metabolic dysfunction-associated steatotic liver disease (MASLD); however early hepatic changes that occur in these infants remain unclear. We integrated metabolomic analysis of umbilical cord plasma and transcriptomic analysis of cord plasma-exposed hepatocytes to examine differences in the intrauterine environment of pregnancies with and without maternal obesity. We identified significantly higher abundance of fatty acids, bioactive lipids, and upregulation of glutathione metabolism in cord plasma from pregnancies with obesity compared to normal weight pregnancies. Hepatocytes exposed to cord plasma from pregnancies with obesity exhibited distinct transcriptional changes that favored cellular injury and inflammation, and impaired hepatocyte development compared to hepatocytes exposed to cord plasma of normal weight pregnancies. In integrated analysis, metabolite-gene relationships were distinct between pregnancies with and without obesity, and the abundance of lipids were positively correlated with the expression of KDM4D, DTX3, and NOTCH4 and negatively correlated with the expression of MT_TS1. Our findings provide novel insights into transcriptional changes induced in hepatocytes by circulating factors in the intrauterine environment of pregnancies with obesity. Excess intrauterine lipids may contribute to hepatic injury, inflammation, impaired mitochondrial function, and impaired hepatocyte development in infants of pregnancies with obesity. - Source: PubMed
Publication date: 2025/07/25
Kozlovich Svetlana YPan Amy YMcIntosh Jennifer JPalatnik AnnaJia ShuangHessner Martin JNghiem-Rao T Hang - Deltex E3 ubiquitin ligase 3 (DTX3) was identified as a tumor suppressor in human cancers. However, whether DTX3 could suppress the progression of bladder cancer (BC) remains unknown. In this study, DTX3 downregulation in BC tissues was confirmed at mRNA and protein levels, and decreased DTX3 expression was associated with poor prognosis. DTX3 knockdown triggered aberrant epithelial-to-mesenchymal transition (EMT), principally via downregulation of E-cadherin and upregulation of N-cadherin, MMP9, Snail, and Slug. Gain- and loss-of-function assays indicated that DTX3 acted as a suppressor gene by inhibiting the migration and invasion of BC cells both in vivo and in vitro. Further analysis revealed that DTX3 inhibited Notch signaling pathway activity, and the Notch signaling inhibitor DAPT could partially reverse the effects of DTX3 knockdown on the metastatic abilities of BC cells. Mechanically, DTX3 bind to Notch intracellular domain (NICD) via its C-terminal RING finger domain (RFD), ubiquitinated, and degraded NICD, resulting in repression of the Notch pathway. Our findings reveal the key role of DTX3 in binding to NICD, promoting its ubiquitination and protein degradation, and suppressing the activation of the Notch signaling pathway to inhibit BC invasion and metastasis. - Source: PubMed
Publication date: 2025/03/23
Cheng YuSun QiChen YaWang JiaYuChen YanJunYang YuanZhongZhang JiangBoCao YunLi ZhiYongZhang YiJun - The recent discovery of non-proteinaceous ubiquitylation substrates broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated via ester bond formation. DTX3L, a member of the DELTEX family E3 ubiquitin ligases, ubiquitylates DNA and RNA in vitro and that this activity is shared with DTX3, but not with the other DELTEX family members DTX1, DTX2 and DTX4. DTX3L shows preference for the 3'-terminal adenosine over other nucleotides. In addition, we demonstrate that ubiquitylation of nucleic acids is reversible by DUBs such as USP2, JOSD1 and SARS-CoV-2 PLpro. Overall, our study proposes reversible ubiquitylation of nucleic acids in vitro and discusses its potential functional implications. - Source: PubMed
Publication date: 2024/09/06
Zhu KangChatrin ChatrinSuskiewicz Marcin JAucagne VincentFoster BenjaminKessler Benedikt MGibbs-Seymour IanAhel DraganaAhel Ivan