Ask about this productRelated genes to: WDR21A antibody
- Gene:
- DCAF4 NIH gene
- Name:
- DDB1 and CUL4 associated factor 4
- Previous symbol:
- WDR21, WDR21A
- Synonyms:
- DKFZp434K114
- Chromosome:
- 14q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-01-15
- Date modifiied:
- 2016-10-05
Related products to: WDR21A antibody
Related articles to: WDR21A antibody
- Hepatocellular carcinoma (HCC) cells sustain viability and radioresistance by actively countering oxidative stress. Understanding the mechanisms regulating reactive oxygen species (ROS) homeostasis is therefore crucial for developing novel therapies. Using integrated genome-wide CRISPR-Cas9 screening coupled with transcriptomic and metabolomic profiling, we identified DDB1 and CUL4-associated factor 4 (DCAF4) as an essential regulator of oxidative stress resistance in HCC. Mechanistically, DCAF4 functions as a CRL4 E3 ligase adapter that promotes KEAP1 ubiquitination and degradation. Notably, under oxidative stress, cytoplasmic stress granules (SGs) form a localized platform that facilitates the DCAF4-KEAP1 interaction, accelerating KEAP1 degradation and leading to NRF2 activation and upregulation of antioxidant genes. We further identified that the transcription factor XBP1 enhances DCAF4 expression. Targeting this axis, we performed computational screening to identify a small-molecule inhibitor that disrupts the DCAF4-KEAP1 interaction. This compound effectively enhanced brachytherapy (BT) sensitivity and inhibited tumor growth in preclinical HCC models. - Source: PubMed
Publication date: 2026/07/14
Huang TianHe YanshuWang XinChenLiu ZhenganQiao EnqiSun TongMei JunhaoDai ShipengWang ZhongkaiFeng ChengCao HengsongWang YimingXia YongxiangLiu EnyuGuo JinheLu Jian - To explore the relationship between the expression levels of DNA damage binding protein 1 and cullin 4-related factor 4 (DCAF4) complex, which degrades the tumor suppressor menin 1 (MEN1)-human telomerase reverse transcriptase (hTERT) axis protein, and the clinicopathological characteristics and prognosis of patients with colon adenocarcinoma. - Source: PubMed
Zhu ShunChen SiyuanZheng QinLiu Hong - Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high cardiovascular risk from Spain. Adherence to the MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations ( < 0.05) between DNAmTL and candidate genes (, , , and ), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR = 0.93; 95% CI: 0.85-0.99; = 0.049 after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta = 0.015; SE: 0.005; = 0.003), indicating that a one-point increase in adherence was related to an average increase of 0.015 ± 0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, "sofrito", and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance ( < 1 × 10) for DNAmTL (intergenics, in the , , and genes) and detected some gene-MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings. - Source: PubMed
Publication date: 2023/11/15
Coltell OscarAsensio Eva MSorlí José VOrtega-Azorín CarolinaFernández-Carrión RebecaPascual Eva CBarragán RocíoGonzález José IEstruch RamonAlzate Juan FPérez-Fidalgo AlejandroPortolés OlgaOrdovas Jose MCorella Dolores - Different drug combinations including irinotecan remain some of the most important therapeutic modalities in treating colorectal cancer (CRC). However, chemotherapy often leads to the acquisition of cancer drug resistance. To bridge the gap between in vitro and in vivo models, we compared the mRNA expression profiles of CRC cell lines (HT29, HTC116, and LoVo and their respective irinotecan-resistant variants) with patient samples to select new candidate genes for the validation of irinotecan resistance. Data were downloaded from the Gene Expression Omnibus (GEO) (GSE42387, GSE62080, and GSE18105) and the Human Protein Atlas databases and were subjected to an integrated bioinformatics analysis. The protein-protein interaction (PPI) network of differently expressed genes (DEGs) between FOLFIRI-resistant and -sensitive CRC patients delivered several potential irinotecan resistance markers: NDUFA2, SDHD, LSM5, DCAF4, COX10 RBM8A, TIMP1, QKI, TGOLN2, and PTGS2. The chosen DEGs were used to validate irinotecan-resistant cell line models, proving their substantial phylogenetic heterogeneity. These results indicated that in vitro models are highly limited and favor different mechanisms than in vivo, patient-derived ones. Thus, cell lines can be perfectly utilized to analyze specific mechanisms on their molecular levels but cannot mirror the complicated drug resistance network observed in patients. - Source: PubMed
Publication date: 2022/07/16
Kryczka JakubBoncela Joanna - Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. In this study, we aimed to explore the role and mechanism of lncRNA ST8SIA6-AS1 in HCC. We found that ST8SIA6-AS1 was upregulated in HCC tissues and associated with poorer overall survival of HCC patients from TCGA. Moreover, ST8SIA6-AS1 was highly expressed in HCC in-house tissues and cells, and ST8SIA6-AS1 upregulation was related to aggressive tumor phenotypes and the poor overall survival of HCC patients. Downregulation of ST8SIA6-AS1 suppressed HCC cell proliferation, migration and invasion in vitro and restrained HCC tumorigenesis in vivo. In terms of mechanism, ST8SIA6-AS1 regulated melanoma-associated antigen (MAGE)-A3 (MAGEA3) and DDB1-and Cul4-associated factor 4-like 2 (DCAF4L2) expression, and rescue experiments verified that ST8SIA6-AS1 played a protumorigenic role in HCC via the regulation of MAGEA3 and DCAF4L2. ST8SIA6-AS1 partly directly bound to miR-129-5p and functioned as a competing endogenous RNA (ceRNA), subsequently facilitating the expression of the miR-129-5p target gene DCAF4L2 to play its role in HCC. In summary, our results identified ST8SIA6-AS1 as an oncogenic lncRNA predicting poor clinical outcomes of patients with HCC. These findings suggest that ST8SIA6-AS1 is a potential therapeutic target for HCC. - Source: PubMed
Publication date: 2020/10/01
Zhang XiufenXu SuiHu CaixiaFang KaiZhou JunjingGuo ZijianZhu GuodingLi Lihua