Ask about this productRelated genes to: WDR32 antibody
- Gene:
- DCAF10 NIH gene
- Name:
- DDB1 and CUL4 associated factor 10
- Previous symbol:
- WDR32
- Synonyms:
- MGC10765, FLJ23201
- Chromosome:
- 9p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-18
- Date modifiied:
- 2015-07-09
Related products to: WDR32 antibody
Related articles to: WDR32 antibody
- Co-translational N-terminal modifications such as methionine excision, acetylation, and myristoylation govern protein stability, localization, and folding. Disruption can expose N-terminal degrons that trigger ubiquitin-mediated degradation, safeguarding the proteome. N-terminal acetylation usually protects proteins from degradation, but can also promote it through the Ac/N-degron pathway. Src-family kinases (SFKs), signaling enzymes implicated in tumorigenesis, require N-terminal myristoylation for function. Using peptide pull-downs, mass spectrometry, and AlphaFold 3 predictions, we identify DCAF10 as the E3 ligase substrate receptor for alternatively N-terminally acetylated SFKs. Combining siRNA-mediated knockdown and CRISPR/Cas9-mediated knockout of endogenous Lyn with inducible Lyn-GFP variants confirms that DCAF10 regulates SFK levels by recognizing an N-terminal acetylated glycine residue. In vitro, a CUL4A-DDB1-DCAF10 complex ubiquitinates N-terminally acetylated SFKs. Thus, we define a novel N-degron pathway that monitors replacement of myristoylation by acetylation and activates degradation of SFKs upon acetylation. This mechanism may extend to other N-terminally myristoylated proteins beyond SFKs. - Source: PubMed
Publication date: 2026/01/03
Kremer NoraMueller FranziskaNguyen HangSchulz LouisaPopp TanjaArtes ElenaWolters JulianRenner MichaelVetter IngridMaffini StefanoRobles Maria SMusacchio AndreaBange Tanja - Understanding the mechanisms underlying Kirsten rat sarcoma (KRAS) mutation-driven development and progression of pancreatic ductal adenocarcinoma (PDAC) may facilitate the discovery of novel strategies for KRAS-mutant PDAC (KRAS-PDAC) treatment. Here, it is reported that downregulation of arachidonate 15-lipoxygenase (ALOX15B) significantly correlated with poor outcomes in patients with KRAS-PDAC. Mechanistically, KRAS/ERK1-elicited phosphorylation of ABHD17C promotes depalmitoylation and membrane-to-cytoplasm translocation of ALOX15B, facilitating proteasome-dependent degradation of ALOX15B via interaction with the E3 ligase complex CUL4/DDB1/DCAF10. Notably, treatment with methyl protodioscin (MPD), a steroid saponin primarily purified from polygonatum sibiricum rhizome, restored the S-palmitoylation and membrane location of ALOX15B via disruption of the ABHD17C/ALOX15B interaction, consequently resulting in significant inhibition of growth rate of patient-derived KRAS-PDAC organoids in vitro and KRAS-PDAC-formed tumor in vivo via induction of ferroptosis. Therefore, these findings unveil a prominent role of ferroptosis evasion in KRAS-PDAC progression and highlight the potential of targeting KRAS/ERK1/ABHD17C/ALOX15B axis in KRAS-PDAC treatment. - Source: PubMed
Publication date: 2025/06/26
Li ManYu XuexinLiu YuanjiOuyang ShuqinWu LongChen XiaohongYu HuiqiChen HaomingLian SenmaoLi ZiwenGong LiyunSong LibingLi Jun - Inactivation of EP300/CREBB paralogous cellular lysine acetyltransferases (KATs) during the early phase of infection is a consistent feature of DNA viruses. The cell responds by stabilizing transcription factor IRF3 which activates transcription of scores of interferon-stimulated genes (ISGs), inhibiting viral replication. Human respiratory adenoviruses counter this by assembling a CUL4-based ubiquitin ligase complex that polyubiquitinylates RUVBL1 and 2 inducing their proteasomal degradation. This inhibits accumulation of active IRF3 and the expression of anti-viral ISGs, allowing replication of the respiratory HAdVs in the face of inhibition of EP300/CBEBBP KAT activity by the N-terminal region of E1A. - Source: PubMed
Publication date: 2023/11/14
Zemke Nathan RHsu EmilyBarshop William DSha JihuiWohlschlegel James ABerk Arnold J - As a major complication after percutaneous coronary intervention (PCI) in patients who suffer from coronary artery disease, in-stent restenosis (ISR) poses a significant challenge for clinical management. A miRNA-mRNA regulatory network of ISR can be constructed to better reveal the occurrence of ISR. The relevant data set from the Gene Expression Omnibus (GEO) database was downloaded, and 284 differentially expressed miRNAs (DE-miRNAs) and 849 differentially expressed mRNAs (DE-mRNAs) were identified. As predicted by online tools, 65 final functional genes (FmRNAs) were overlapping DE-mRNAs and DE-miRNAs target genes. In the biological process (BP) terms of gene ontology (GO) functional analysis, the FmRNAs were mainly enriched in the cellular response to peptide, epithelial cell proliferation, and response to peptide hormone. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the FmRNAs were mainly enriched in breast cancer, endocrine resistance, and Cushing syndrome. Jun proto-oncogene, activator protein-1 (AP-1) transcription factor subunit (), insulin-like growth factor 1 receptor (), member oncogene family (), specificity protein 1 (), protein tyrosine phosphatase nonreceptor type 1 (), DDB1 and CUL4 associated factor 10 (), retinoblastoma-binding protein 5 (), and eukaryotic initiation factor 4A-I () were hub genes in the protein-protein interaction network (PPI network). The miRNA-mRNA network containing DE-miRNAs and hub genes was built. Hsa-miR-139-5p-, hsa-miR-324-5p- axis pairs were found in the miRNA-mRNA network, which could promote ISR development. The aforementioned results indicate that the miRNA-mRNA network constructed in ISR has a regulatory role in the development of ISR and may provide new approaches for clinical treatment and experimental development. - Source: PubMed
Publication date: 2022/08/15
Song LinghongFeng YufeiTian FengLiu XiaoangJin ShanWang ChengyanTang WuyueDuan JuncangGuo NaShen XihuaHu JianmingZou HongGu WenyiLiu KejianPang Lijuan - Ovarian cancer is a common gynecological malignant tumor that greatly threatens women's health, so we screened potential biomarkers of ovarian cancer and analyzed their prognostic value. - Source: PubMed
Li HuiqinLi MingTang ChunhuiXu Liang