Ask about this productRelated genes to: DCUN1D1 antibody
- Gene:
- DCUN1D1 NIH gene
- Name:
- defective in cullin neddylation 1 domain containing 1
- Previous symbol:
- -
- Synonyms:
- RP42, SCRO, DCUN1L1, Tes3, SCCRO
- Chromosome:
- 3q26.33
- Locus Type:
- gene with protein product
- Date approved:
- 2005-07-11
- Date modifiied:
- 2016-10-05
Related products to: DCUN1D1 antibody
Related articles to: DCUN1D1 antibody
- Resistance to monotherapy remains a major challenge in the treatment of nonsmall cell lung cancer (NSCLC), highlighting the need for innovative therapeutic strategies. To address this issue, we developed a dual-targeting strategy aimed at simultaneously inhibiting the oncogenic protein-protein interaction (PPI) between UBE2M and DCN1─which is critical for neddylation-dependent activation of cullin-RING ligases (CRLs)─and histone deacetylase (HDAC) activity. Inspired by the synergistic antitumor effects observed with combined inhibition of UBE2M-DCN1 and HDAC, we designed hybrid molecules integrating pharmacophores targeting both pathways. Our preferred compound JN210 effectively disrupts the UBE2M-DCN1 interaction and inhibits HDAC, demonstrating significantly enhanced cytotoxicity compared to the parent compounds in vitro and potent tumor growth suppression in vivo. Mechanistic studies revealed dual blockade of CRL neddylation and induction of histone hyperacetylation, resulting in impaired DNA damage repair and synergistic apoptosis. As a novel DCN1/HDAC dual inhibitor, JN210 represents a promising therapeutic candidate for NSCLC. - Source: PubMed
Zheng TaoLi YiguiHuang YunyuanHe LinchongHuang XiaojieFan CongWen JuqiXu JunSun Ping-HuaChen Wen-HuaChen Xin - [This retracts the article DOI: 10.3727/096504017X14920318811712.]. - Source: PubMed
Publication date: 2026/03/23
- E3 ligases partner with E2 enzymes to regulate vast eukaryotic biology. The hierarchical nature of these pairings, with >600 E3s and ~40 E2s in humans, necessitates that E2s cofunction with numerous different E3s. Here, focusing on E3s in the RING-between-RING (RBR) family and their partner UBE2L3 and UBE2D-family E2s, we report an approach to interrogate selected pathways. We screened phage-displayed libraries of structure-based E2 variants (E2Vs) to discover enzymes with enhanced affinity and specificity toward half of all RBR E3 ligases (ARIH1, ARIH2, ANKIB1, CUL9, HOIL1, HOIP, and RNF14). Collectively, these E2Vs allowed distinguishing actions of different cofunctioning E3s, obtaining high-resolution cryogenic Electron Microscopy (cryo-EM) structures of an RBR E3 in the context of a substrate-bound multiprotein complex, and profiling an endogenous RBR E3 response to an extracellular stimulus. Overall, we anticipate that E2V technology will be a generalizable tool to enable in-depth mechanistic and structural analysis of E3 ligase functions, and mapping their activity states and protein partners in cellular signaling cascades. - Source: PubMed
Publication date: 2026/01/02
Du JialeAndree Gisele AHorn-Ghetko DanielStier LucaSingh JaspalKostrhon SebastianKiss LeoMann MatthiasSidhu Sachdev SSchulman Brenda A - Colorectal cancer (CRC) is the third most common malignancy worldwide, and the five-year survival rate for patients with metastatic disease remains below 15% despite advances in current therapeutic approaches. Post-translational modifications (PTMs) play a pivotal role in CRC initiation and progression, among which neddylation—a critical ubiquitin-like modification—is closely associated with tumor cell proliferation, migration, and chemotherapy resistance. This modification covalently attaches neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to lysine residues of substrate proteins, thereby regulating protein stability, DNA repair, and immune responses. In CRC, key enzymes in the neddylation pathway, such as NAE1, UBE2M, and DCUN1D1, are frequently aberrantly activated, leading to the stabilization of key oncoproteins and cell-cycle regulators by preventing their ubiquitin-mediated degradation, thereby promoting tumor progression and drug resistance. Although neddylation has been extensively studied in various cancer types, its precise role in CRC has not been fully elucidated. Recent studies have shown that targeting neddylation—particularly with NAE1 inhibitors such as MLN4924—can significantly suppress tumor progression and offer new therapeutic opportunities to overcome chemoresistance. This review systematically summarizes the roles of neddylation in CRC pathogenesis, chemoresistance, and immune microenvironment remodeling, with a focus on the clinical potential of combining neddylation-targeted inhibitors with chemotherapy and immunotherapy, as well as the prospective application of liquid biopsy in precision monitoring, aiming to provide a theoretical basis and future directions for molecular targeted therapy and clinical translation in CRC. - Source: PubMed
Publication date: 2025/12/13
Mi ChenCui FengWang SiyangDu YongyueLi YongzhaoYang Hanteng - Vitiligo is a skin disorder marked by the loss of pigmentation due to melanocyte destruction. Our previous study demonstrated that DCUN1D1 is a novel regulator of CXCL10 and is associated with mitochondrial dysfunction. RNA-seq data revealed that the expression of Parkin, a mitophagy-related molecule, is decreased in vitiligo patients. Parkin functions as an E3 ubiquitin ligase. Based on these findings, we hypothesize that Parkin ubiquitinates DCUN1D1, thereby influencing the level of CXCL10 during the progression of vitiligo. Parkin and DCUN1D1 expression levels were assessed in both vitiligo patients and mice. To examine interactions, HaCaT cells were transfected with Flag-DCUN1D1, Myc-PRKN, or HA-Ub, followed by coimmunoprecipitation (co-IP) and Western blotting analysis. Mitochondrial activity and mitophagy were evaluated following various treatments, including the use of CCCP. HaCaT cells were transfected with DCUN1D1 or different concentrations of Parkin to assess CXCL10 levels. The supernatant from HaCaT cells was collected and incubated with melanocytes for 48 h, after which the apoptosis level was examined. DCUN1D1 was found to be upregulated, whereas Parkin was downregulated in both vitiligo patients and mice. Parkin interacts with DCUN1D1 and ubiquitinates it at lysine 27 (K27). Increased levels of Parkin counteract the reductions in mitochondrial activity and mitophagy induced by DCUN1D1, significantly downregulate CXCL10 levels, and reduce melanocyte apoptosis. This study provides evidence that Parkin-mediated ubiquitination of DCUN1D1 regulates CXCL10 levels in vitiligo, thereby offering a new experimental foundation for understanding the pathogenesis of vitiligo. - Source: PubMed
Jin ShiyuDong TingruLi YujieYang FenglanXiong RenxueSong XiuzuGuan Cuiping