Ask about this productRelated genes to: FBXW8 Blocking Peptide
- Gene:
- FBXW8 NIH gene
- Name:
- F-box and WD repeat domain containing 8
- Previous symbol:
- FBXO29
- Synonyms:
- FBX29, FBW6, FBW8
- Chromosome:
- 12q24.22
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-27
- Date modifiied:
- 2015-08-25
Related products to: FBXW8 Blocking Peptide
Related articles to: FBXW8 Blocking Peptide
- Cervical cancer is one of the major threats to women's health worldwide. Nuclear Cap Binding Protein 2(NCBP2) plays a significant role in various cancers, and mitophagy, as a cellular homeostasis regulation mechanism, is closely related to tumorigenesis and development. However, the specific mechanisms by which NCBP2 regulates mitophagy in cervical cancer remain unclear. Bioinformatics was used to screen cervical cancer-related genes and mechanisms. The effects of NCBP2 on the viability, migration, and mitochondrial function of cervical cancer cells were investigated using CCK-8, EdU, and Transwell assays. Comprehensive experimental methods, including RT-qPCR and Western blot, were employed to elucidate the potential mechanisms of NCBP2. NCBP2 was found to be significantly upregulated in cervical cancer and promoted the in vitro proliferation, migration, and invasion of cervical cancer cells. Mechanistically, NCBP2 regulated the alternative splicing of KIF23 to facilitate cervical cancer progression. NCBP2 also regulated mitophagy in cervical cancer cells via the KIF23-PGAM5 axis. Moreover, FBXW8 inhibited the overactivation of mitophagy and exerted tumor-suppressive effects by ubiquitinating and degrading NCBP2. This study reveals that NCBP2 regulates alternative splicing and mitophagy to influence cervical cancer progression, providing new potential therapeutic targets and strategies for cervical cancer treatment. - Source: PubMed
Publication date: 2026/03/24
Su YingZhang JuxinWu HenghuiZhang YuZhou Wenlei - Pancreatic adenocarcinoma (PAAD) lacks effective therapies due to complex macromolecular signaling networks. Here, we identified the natural compound Trienomycin A (TA) as a potent binder and degrader of the key signaling adaptor protein Insulin Receptor Substrate 1 (IRS1), disrupting its macromolecular assembly in insulin-like growth pathways. Through integrated biochemical, cellular, and in vivo analyses, we demonstrated that TA directly bound the phosphotyrosine-binding (PTB) domain of IRS1, inducing proteasomal degradation of this critical macromolecular hub mediated by the E3 ubiquitin ligase FBXW8. This degradation suppressed IRS1-mediated PI3K/Akt/mTOR signaling complex formation, leading to mTOR inhibition. Surprisingly, this dysregulation of IRS1-dependent macromolecular networks elicited cytoprotective autophagy-a resistance mechanism evidenced by impaired autophagic flux upon pharmacological or genetic autophagy blockade. Crucially, IRS1 ablation phenocopied TA's effects on autophagy and tumor suppression, while IRS1 overexpression conferred resistance, establishing IRS1 as TA's primary macromolecular target. Our work revealed that TA-induced IRS1 degradation drives mTOR-dependent cytoprotective autophagy, attenuating its anti-tumor efficacy. Furthermore, the E3 ubiquitin ligase FBXW8 was identified as an endogenous inhibitor of IRS1 via ubiquitination analysis. Mechanistically, FBXW8 bound to IRS1 and promoted its ubiquitination, thereby accelerating its degradation. These findings provide a mechanistic rationale for co-targeting IRS1 and autophagy-associated macromolecular complexes to overcome therapeutic resistance in PAAD. - Source: PubMed
Publication date: 2025/09/08
Li Meng-JiaoZhang RuiSheikho AlmutamadTang Jiang-JiangGao Yu-QiHuang Wei-WeiGao Jin-Ming - - Source: PubMed
Publication date: 2025/08/20
Lin PingFu JiejunZhao BinjiahuiLin FengZou HaifengLiu LeiyuZhu ChengWang HongmeiYu Xiaoguang - Nanog is a key transcription factor that regulates the self-renewal and pluripotency of embryonic stem cells (ESCs). Although Kap1 has been demonstrated to regulate the stability of stemness factors, including Oct4 and Lin28A, its role in regulating Nanog protein stability in ESCs remains unexplored. In the present study, we examined the interaction between Kap1 and Nanog and its role in stabilizing the Nanog protein. Immunoprecipitation assays revealed that Nanog specifically interacted with the coiled-coil domain of Kap1. Kap1 overexpression increased the stability of the Nanog protein by inhibiting its ubiquitination and proteasomal degradation, whereas Kap1 silencing accelerated Nanog degradation. Furthermore, Kap1 overexpression inhibits Nanog degradation by interfering with the binding of Nanog to Fbxw8, an E3 ubiquitin ligase that promotes Nanog degradation via a proteasome-dependent process. These results indicate that Kap1 acts as a key regulator to preserve ESC properties by modulating the protein stability of stemness factors, including Oct4, Lin28A, and Nanog. - Source: PubMed
Publication date: 2025/08/05
Moon Hye JiLee NayeonLee Bo SeokPark Min SeokJung Yoon JiKim Ye SeulKim Jae Ho - Ewe longevity indicators are complex traits that are lowly heritable, expressed late in life, and sex-limited, making them challenging to include in breeding programs. In this context, genome-wide association studies (GWASs) can provide more information on the complex genetic control of these traits. Therefore, the primary objective of this study was to carry out association analyses for 8 longevity-related traits in 12,734 Katahdin ewes. A total of 126 associations at the chromosome-wide level and 3 at genome-wide level were found. These associations involved 86 single-nucleotide polymorphisms (SNPs) located across 22 chromosomes, with 24 of these SNPs associated with two or more traits. The variants overlapped with genes previously associated with prolificacy (, , , , and ), ovarian follicle pool (, , and ), synthesis and release of reproductive hormones (, , and ), and early pregnancy events (, , , , , , , , and ). Moreover, genes related to response to stress or pathological conditions (, , , , , , , , , , , , , and zinc-finger proteins), growth performance (, , , and ), and carcass traits ( and ) were also implicated. Metabolic pathways such as oxytocin signaling and cardiac-related pathways were enriched. These findings suggest that longevity indicators in Katahdin ewes are highly polygenic traits influenced by a combination of voluntary and involuntary culling reasons. Candidate genes and metabolic pathways influencing reproductive performance and health may play a key role in the functional longevity of Katahdin ewes. - Source: PubMed
Publication date: 2025/07/03
Pinto Luis F BLewis Ronald MRocha Artur OFreking Brad AMurphy Tom WWilson Carrie SNilson Sara MBurke Joan MBrito Luiz F