Ask about this productRelated genes to: FBXO24 antibody
- Gene:
- FBXO24 NIH gene
- Name:
- F-box protein 24
- Previous symbol:
- -
- Synonyms:
- FBX24
- Chromosome:
- 7q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-27
- Date modifiied:
- 2016-10-05
Related products to: FBXO24 antibody
Related articles to: FBXO24 antibody
- The etiology of non-obstructive azoospermia (NOA) remains largely idiopathic, emphasizing the urgent need for molecular biomarkers to predict sperm retrieval outcomes. Here, we integrate bioinformatic analyses of public transcriptomic data with experimental expression profiles to investigate a potential regulatory network involving hsa-circ_0081481, miR-3960 and FBXO24 in NOA. Seven GEO datasets were analyzed to identify differentially expressed genes, and FBXO24 was found to be a consistently downregulated gene in NOA. Upstream regulators and interacting non-coding RNAs were predicted, leading to the selection of miR-3960 (a microRNA targeting FBXO24) and hsa-circ_0081481 (a circular RNA predicted to sponge miR-3960). Subsequently, FBXO24, miR-3960 and hsa-circ_0081481 expression levels were measured in the plasma of 60 men with NOA (categorized by histopathology and sperm retrieval outcome) and 40 fertile controls. FBXO24 and hsa-circ_0081481 were significantly downregulated in NOA (especially in hypospermatogenesis and maturation arrest), whereas miR-3960 was significantly upregulated in these subgroups. Of note, hsa-circ_0081481 achieved excellent diagnostic performance (AUC 0.920) in distinguishing NOA cases with successful and failed sperm retrieval, respectively. miR-3960 also showed high accuracy (AUC 0.861) after its inverse expression pattern was taken into account, and FBXO24 showed moderate predictive value. Our findings suggest that the hsa-circ_0081481/miR-3960/FBXO24 axis is dysregulated in NOA and may serve as a novel trio of non-invasive biomarkers. This study provides new insights into the molecular mechanisms of spermatogenic failure in NOA and provides a basis for improved diagnosis and personalized fertility treatment. - Source: PubMed
Publication date: 2026/05/21
Babakhanzadeh EmadKhodadadian AliEsmaeili Dahaj ForouzanSolatzadeh HormozNazari MajidMozhdeh MahyaVahidi Mehrgardi SerajoddinJafari Mohammad HassanDehghani MohammadrezaGhafouri-Fard SoudehGhasemi Nasrin - Dysregulation of MYC proto-oncogene, bHLH transcription factor (MYC) represents a common yet mechanistically unresolved driver of hepatocellular carcinoma (HCC). While MYC remains an elusive therapeutic target, developing strategies to promote its degradation emerges as a promising alternative approach. Here we show that vaccinia-related kinase 2 (VRK2) functions as a direct MYC-interacting kinase that stabilizes the oncoprotein through phosphorylation at Serine (Ser)281/293. This phosphorylation enables VRK2 to compete with the Skp1-Cullin-F-box protein complex containing FBXO24 (SCF-FBXO24) E3 ligase, thereby blocking MYC polyubiquitination and proteasomal degradation. The stabilized MYC-VRK2 complex amplifies transcriptional activation of protumorigenic programs, including the immune checkpoint programmed cell death ligand 1 (PD-L1) and VRK2 itself, establishing a self-reinforcing oncogenic circuit. Therapeutic inhibition of VRK2 in HCC models reduces MYC protein levels, suppresses tumor progression, and synergizes with anti- programmed cell death-1 (PD-1) immunotherapy. Our results reveal VRK2-mediated stabilization of MYC as a critical nexus linking hepatocarcinogenesis to immune evasion, proposing VRK2 kinase inhibition as a mechanism-based therapeutic strategy for MYC-driven HCC. - Source: PubMed
Publication date: 2025/10/10
Su ChenLiao ZhibinMo JieLiu FurongWang WeijianZhang HaoquanZhang HongweiLiu YachongPan YonglongZhu HeChen XiaopingZhang ZhanguoZhu PengZhang Bixiang - Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targetable proteins for treatment. PARP inhibitors (PARPi) are effective in BRCA-mutated cancers but have limited utility in non-germline BRCA-mutated (non-gBRCAm) TNBC. We hypothesized that inducing BRCAness by targeting RAD51, a key homologous recombination protein, could sensitize non-gBRCAm TNBC to PARPi. - Source: PubMed
Publication date: 2025/08/05
Tsoi HoLeung George Man HongMan Ellen Pui SumYou Chan PingCheung Koei Ho LamChan Kelvin Yuen KwongGong ChunHuen Michael Shing YanKhoo Ui Soon - Asthenozoospermia is one of the major causes of male infertility, typically resulting from malformed flagella and dysfunctional mitochondria. However, the pathogenic mechanisms underlying asthenozoospermia remain unclear. Here, we show that FBXO24, a F-box protein within the SCF E3 ubiquitin ligase complex, is required for maintaining mitochondrial function and ATP production during spermiogenesis. Using Fbxo24 knockout mice, we demonstrate that the depletion of FBXO24 leads to male infertility due to a malformed sperm head and severe motility defects. The decreased motility resulted from dysfunction of mitochondria that was characterized by disorganized mitochondrial clustering, reduced mitochondrial membrane potential and elevated reactive oxygen species levels. Based on quantitative proteomics, we identified SLC25A26, a mitochondrial S-adenosylmethionine transporter, as a previously unreported substrate for FBXO24. Mechanistically, FBXO24 mediates K6-linked polyubiquitylation of SLC25A26 at lysine residue 31, targeting it for degradation. Elevated SLC25A26 induced mitochondrial fragmentation, suppressed glycolysis and oxidative phosphorylation, and decreased ATP production. All these results suggest that FBXO24 safeguards mitochondrial integrity by controlling SLC25A26 stability, ensuring ATP production for sperm motility. It also suggests that some mutations of FBXO24 might be associated with asthenozoospermia in human. - Source: PubMed
Publication date: 2025/08/04
Zheng YunlongWu BingbingDong FuchengJiang YiranLong ChenghongLiu JiayiZhang YanZhao JianguoLi Wei - Forkhead Box Protein P1 (FoxP1) is a crucial transcriptional repressor essential for the development of the brain and heart. In adults, FoxP1 protein levels are dysregulated in a variety of disorders, including chronic obstructive pulmonary disease (COPD), atherosclerosis, and heart failure, where they causally contribute to disease pathogenesis. Although independent investigators have reported that FoxP1 protein is ubiquitinated, and E3 ligases have been identified for other FoxP family proteins, the identity of the E3 ligase that controls FoxP1 protein stability has remained unknown. Here, we identify FBXO24, a subunit of the Skp-Cullin-F-box (SCF) ubiquitin E3 ligase complex, as the regulator of FoxP1 ubiquitination and stability. Specifically, FBXO24 regulates K48 and K63 ubiquitination, complexes with, and co-localizes to the nucleus with FoxP1 protein in lung epithelial cells. Depleting FBXO24 reverses the unfolded protein response and cell death triggered by loss of FoxP1 protein in lung epithelium, suggesting a protective role. Additionally, FBXO24 knockout mice exhibit elevated FoxP1 levels in the lung and heart and reduced unfolded protein response activity after short-term cigarette smoke exposure. Intriguingly, we also uncovered bidirectional regulation, whereby FoxP1 protein binds to the FBXO24 promoter to suppress FBXO24 transcription. To our knowledge, this is the first evidence that a substrate for an E3 ligase can also regulate the E3 ligase and, therefore, control levels of other substrates, revealing new regulatory networks. Targeting FBXO24 may offer a therapeutic strategy for COPD, atherosclerosis, and heart failure by stabilizing FoxP1 levels in the heart and lungs and mitigating harmful downstream effects. - Source: PubMed
Publication date: 2025/05/28
Maloy AbigailWalter SydneyMascilli ArthurKlein David CLardo Santana MLondino JamesNyunoya ToruMcDyer JohnSun MiaZeng XuemeiYates NathanCantrell PamelaHainer Sarah JMallampalli Rama KChandra Divay