Ask about this productRelated genes to: FBXO24 Blocking Peptide
- 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 Blocking Peptide
Related articles to: FBXO24 Blocking Peptide
- 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 - Ribonucleoprotein (RNP) granules are membraneless electron-dense structures rich in RNAs and proteins, and involved in various cellular processes. Two RNP granules in male germ cells, intermitochondrial cement and the chromatoid body (CB), are associated with PIWI-interacting RNAs (piRNAs) and are required for transposon silencing and spermatogenesis. Other RNP granules in male germ cells, the reticulated body and CB remnants, are also essential for spermiogenesis. In this study, we disrupted FBXO24, a testis-enriched F-box protein, in mice and found numerous membraneless electron-dense granules accumulated in sperm flagella. knockout (KO) mice exhibited malformed flagellar structures, impaired sperm motility, and male infertility, likely due to the accumulation of abnormal granules. The amount and localization of known RNP granule-related proteins were not disrupted in KO mice, suggesting that the accumulated granules were distinct from known RNP granules. Further studies revealed that RNAs and two importins, IPO5 and KPNB1, abnormally accumulated in KO spermatozoa and that FBXO24 could ubiquitinate IPO5. In addition, IPO5 and KPNB1 were recruited to stress granules, RNP complexes, when cells were treated with oxidative stress or a proteasome inhibitor. These results suggest that FBXO24 is involved in the degradation of IPO5, disruption of which may lead to the accumulation of abnormal RNP granules in sperm flagella. - Source: PubMed
Publication date: 2024/08/20
Kaneda YukiMiyata HaruhikoXu ZoulanShimada KeisukeKamoshita MakiNakagawa TatsuyaEmori ChihiroIkawa Masahito