Ask about this productRelated genes to: FBXO42 Blocking Peptide
- Gene:
- FBXO42 NIH gene
- Name:
- F-box protein 42
- Previous symbol:
- -
- Synonyms:
- KIAA1332, Fbx42
- Chromosome:
- 1p36.13
- Locus Type:
- gene with protein product
- Date approved:
- 2004-06-15
- Date modifiied:
- 2016-10-05
Related products to: FBXO42 Blocking Peptide
Related articles to: FBXO42 Blocking Peptide
- Protein phosphatase 2A (PP2A) is a Ser/Thr phosphatase that regulates the phosphorylation of almost all cellular processes, including cell division and proliferation. PP2A forms heterotrimeric holoenzyme complexes comprising a catalytic subunit (PP2Ac), a scaffolding subunit (PP2Aa) and variable B regulatory subunits that exert precise control over enzyme substrate specificity and prevent indiscriminate dephosphorylation of phosphoproteins. However, the mechanisms that control the activity of uncomplexed catalytic subunits have remained relatively unclear. Here we find that the E3 ligase SKP1-CUL1-F-box (SCF) complex containing F-box other protein 42 (FBXO42, also known as JFK; hereafter, SCF) degrades holoenzyme-free PP2Ac in a complex with the coiled-coil protein CCDC6 to maintain cancer cell fitness. The cryo-electron microscopy structure of the FBXO42-CCDC6-PP2Ac assembly reveals a pseudosymmetric architecture in which CCDC6 forms a central dimeric template that recruits multiple copies of PP2Ac and creates a substrate for FBXO42. Both the quaternary structure of this CCDC6-PP2Ac heterodimer and the post-translationally methylated tail of PP2Ac are recognized by FBXO42 for ubiquitination. The multivalent structure facilitated by CCDC6 enables the assembly of multiple degradation complexes along a single coiled coil, leading to the turnover of free phosphatases and downregulation of catalytic activity. Together, our findings define a mechanism for PP2A control through the ubiquitin-proteosome system and establish a paradigm for cullin-RING ligase-substrate interactions. - Source: PubMed
Publication date: 2026/04/15
Coassolo SebastienMichaelian NairieMaculins TimursAzumaya Caleigh MCheung Tommy KYin JianpingZilberleyb InnaPahuja Kanika BajajGarner ThomasLau TedMau DavisGrimmer MatthewFortin Jean-PhilippeCosta MikeDimitrova Yoana NRose Christopher MHsu Peter LYauch Robert L - F-box proteins are the substrate recognition modules of the SCF (SKP1-Cullin-F-box) E3 ubiquitin ligase complex. FBXO42, an understudied member of this family, has recently emerged as a modulator of key cellular processes, including cell cycle progression, the DNA damage response, and glioma stem cell survival. In this study, we define the function of FBXO42 as a major regulator of the protein phosphatase PP4. Phosphoprotein phosphatases (PPPs) have a broad array of substrates, hence necessitating tight regulation. We observe that FBXO42 ubiquitinates the PP4 complex to govern the assembly of regulatory and catalytic subunits, with the net effect of restraining the latter's phosphatase activity. FBXO42 depletion unleashes PP4 activity, with broad cellular effects, highlighting FBXO42 as a novel regulatory node in ubiquitin-mediated signalling for future therapeutic exploitation. - Source: PubMed
Publication date: 2026/01/03
Yang HongbinSmith PaulMa YingyingSouthworth EmilyGopala Krishna VarunSalerno BeatriceRowland JosephLoftus Alexander E PGrieco DomenicoVendrell IolandaFischer RomanKessler Benedikt MD'Angiolella Vincenzo - One of the most powerful tools for identifying genomic regions associated with various phenotypes is GWAS. Identifying genes influencing milk production traits in Iranian Holstein dairy cows is crucial to understanding the genetic mechanisms underlying these traits and improving future milk production. Therefore, using a single-step GWAS, this study aimed to identify genomic regions, genes, and pathways associated with milk yield (MY), milk fat percentage (FP), milk protein percentage (PP), and somatic cell count (SCC) traits in the Iranian Holstein cattle population. In this study, 210 animals were genotyped using 30K (150 animals from Herd 1) and 50K (60 animals from Herd 2) SNP arrays. Genotypes were then imputed to whole-genome sequence level using the 1000 Bull Genomes Project reference panel, resulting in 6,583,595 high-confidence imputed SNPs forGWAS analysis. Genomic regions associated with milk production traits included 184 significant SNP markers (milk yield, milk fat, milk protein, and somatic cell count, with 86, 18, 22, and 58 significant SNP markers, respectively) based on a significance threshold of P value < 1 × 10⁻⁸ across 10 chromosomes (2, 5, 7, 17, 19, 21, 24, 26, and 28). For the traits FP, PP, MY, and SCS, 5, 6, 9, and 7 candidate genes were identified near the significant SNPs, respectively. Key genes with important biological roles included ATE1, FGFR2, ALDH1A3, CHSY1, GABRG3, FBXO36, PID1, TRIP12, CD52, WDTC1, MATN1, CIDEA, LYZ, CPM, FBXO42, MAML3, SGMS2, HADH, CYP2U1, SCLT1 and THRSP. Therefore, the ATE1, FGFR2, and LYZ genes is not only a key marker for udder health and milk quality but also a promising candidate for genomic selection and therapeutic applications aimed at improving disease resistance in dairy herds. Our research led to the discovery of novel SNPs linked to milk production traits, which could be valuable for future livestock breeding programs. - Source: PubMed
Publication date: 2025/09/01
Maddahi NargesSadeghi MostafaSarghale Ali JalilSaatchi MahdiDavar Siar Mohammad KazemKholghi Muna - Hepatocellular carcinoma (HCC), one of the most common malignancies, accounts for about 80% of all primary liver cancers. FBXO42 belongs to the F-box protein family and functions as a key component of the SCF (Skp1-Cullin-F-box) ubiquitin ligase complex, which is involved in the process of protein ubiquitination. The studies on the role of FBXO42 in different diseases are inadequate, especially in HCC. - Source: PubMed
Publication date: 2025/08/21
Zhou BingWu ShashaHong ShengqianLi HanJiang ZhiSun YongQiu JiannanQin Lei - The Unfolded Protein Response (UPR) is activated by the accumulation of misfolded proteins in the Endoplasmic Reticulum (ER), a condition known as ER stress. Prolonged ER stress and UPR activation cause cell death, by mechanisms that remain poorly understood. Here, we report that regulation of Ataxin-2 by Fbxo42 is a crucial step during UPR-induced cell death. From a genetic screen in Drosophila, we identify loss of function mutations in Fbxo42 that suppress cell death and retinal degeneration induced by the overexpression of Xbp1, an important mediator of the UPR. We identify the RNA binding protein Ataxin-2 as a substrate of Fbxo42, which, as part of a Skp-A/Cullin-1 complex, promotes the ubiquitylation and degradation of Ataxin-2. Upon ER-stress, the mRNA of Xbp1 is sequestered and stabilized in Ataxin-2 granules, where it remains untranslated. Fbxo42 recruitment to these granules promotes the degradation of Ataxin-2, allowing for the translation of Xbp1 mRNA and triggering cell death during the terminal stages of UPR activation. - Source: PubMed
Publication date: 2025/08/13
Santos Cristiana CSchweizer NadineCairrão FátimaRamirez JuanmaOsinalde NereaYang MingGaspar Catarina JRasheva Vanya ITrigo Miguel LHensel ZachAdrain ColinCordeiro Tiago NVoigt FrankaGameiro Paulo AMayor UgoDomingos Pedro M