Ask about this productRelated genes to: FATE1 Blocking Peptide
- Gene:
- FATE1 NIH gene
- Name:
- fetal and adult testis expressed 1
- Previous symbol:
- -
- Synonyms:
- FATE, CT43
- Chromosome:
- Xq28
- Locus Type:
- gene with protein product
- Date approved:
- 2004-09-01
- Date modifiied:
- 2015-08-25
Related products to: FATE1 Blocking Peptide
Related articles to: FATE1 Blocking Peptide
- Dynamic assembly of the complex I signalosome mediated by three death domain (DD)-containing proteins-TNFR1, TRADD and RIPK1-is key for transmitting extracellular TNF stimuli to intracellular NF-κB signalling in controlling 'live or die' cell fate. This signalling hub features the rapid recruitment of TRADD and RIPK1 after engagement of TNFR1 by TNF for the formation of complex I, followed by timed disassembly for transition into downstream signalling complexes, but the mechanism driving the dynamic reversibility of complex I remains unclear. Here we captured the assembly core of complex I and determined its cryo-electron microscopy structure, showing a pentameric fibre comprising 31 DDs, with a single layer of a TRADD-DD pentamer sandwiched between multiple layers of TNFR1-DD and RIPK1-DD homopentamers. Structural analysis revealed a strong opposing electric dipole moment (EDM) generated by RIPK1-DD oligomerization relative to that of TNFR1-DD and TRADD-DD. Structure-guided mutagenesis in TNFR1-TRADD-RIPK1 pentameric fibres altering the EDM without affecting DD oligomerization demonstrated the role and mechanism of EDM in driving the dynamic reversibility mediating the rapid assembly and disassembly of complex I. Our study demonstrates a role for long-range interactions mediated by protein EDMs in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling. - Source: PubMed
Publication date: 2026/04/01
Liu JianpingZhao JingGao JiayangZhao KunHan YaoyaoYang JingLi ZefeiYe JianyuSun ZiyuWang FengyiLiu XinyiLi ZekaiJi SiyuLiu BoLiu CongZhang YixiaoYuan JunyingChou James J - Mitotane is an inhibitor of sterol O-acyltransferase 1 (SOAT1) approved for the treatment of adrenocortical carcinoma (ACC). In cells, mitotane increases reactive oxygen species, lipid peroxidation, and ultimately cell death. This mechanism is similar but distinct from ferroptosis, a cell death mechanism adrenal cortex cells are endogenously predisposed to. Both Acyl-CoA-Synthetase 4 (ACSL4), essential for ferroptosis, and SOAT1 are localized in mitochondria-associated membranes (MAM), specialized contact sites between mitochondria and endoplasmic reticulum (ER). Here, we used protein and lipid mass spectrometry to explore the role of MAMs in adrenocortical cell death. MAMs were isolated from NCI-H295S cells treated with mitotane, the ferroptosis inducer RSL3, or control. Western blotting of marker proteins was used for quality control prior to lipid and protein mass spectrometry. MAM fractions showed strong enrichment of SOAT1 and FATE1 (fetal and adult testis expressed 1) marker proteins, contained ACSL4, and were depleted from mitochondrial MTCO2 independent of treatment condition. Protein mass spectrometry identified IRE1alpha/ERN1, and PERK/EIF2AK3 implicated in the response to mitotane. Proteins involved in ER- and mitochondria-related processes were functionally enriched. We discovered the guanosine nucleotide exchange factor GRIPAP1 in MAMs of mitotane but not RSL3- or control-treated samples. In NCI-H295S cells mitotane upregulated GRIPAP1 expression. Mitotane but not RSL3 pronouncedly reduced the quantity of ubiquinone (Q10) and heme B in MAMs. In conclusion, locally reduced Q10 in MAM may contribute to impaired respiratory chain activity and free radical excess induced by mitotane. Recruitment of GRIPAP1 protein to MAMs may transduce cell death. - Source: PubMed
Publication date: 2025/12/05
Krüger Alexander FSchmitz WernerLamer StephanieTriebig AlexandraMaier TanjaFuss Carmina TAngeli José Pedro FriedmannSchlosser AndreasStigloher ChristianFassnacht MartinWeigand IsabelKroiss Matthias - Sodium-glucose cotransporter 2 (SGLT2) inhibitors have renoprotective properties in diabetic kidney disease (DKD) that extend beyond blood glucose-lowering effects; however, the underlying mechanism remains unclear. Recent studies suggest that the altered homeostasis of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) was closely associated with the progression of DKD. In the current study, we investigated the effects of canagliflozin on diabetic podocyte injury and MAM formation in db/db mice and high glucose-induced podocytes. Eight weeks of canagliflozin treatment (30 mg/kg/day) decreased body weight and blood glucose level, and urinary albumin excretion of diabetic mice. Diabetes-associated renal histopathological changes and podocyte injury of db/db mice were also obviously improved by canagliflozin. In addition, a significant decrease in the MAM area and an increase in the fragmented mitochondria were observed in the podocytes of diabetic kidneys, while canagliflozin enhanced MAM formation and decreased fragmented mitochondria. Furthermore, canagliflozin-treated diabetic mice presented with amelioration of mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and apoptosis. Interestingly, no significant difference was observed after insulin treatment, although its glucose-lowering effect was comparable to that of canagliflozin. In vitro, canagliflozin reversed HG-induced MAM disruption, fragmented mitochondria, podocyte injury, mitochondrial dysfunction, ER stress, and apoptosis in podocytes. However, the above beneficial effects of canagliflozin on podocytes were offset by co-overexpression of FATE1, an uncoupler of MAM, under HG conditions. Taken together, these findings indicate that canagliflozin improves diabetic podocyte injury via modulating MAM structure and function. - Source: PubMed
Publication date: 2025/07/31
Zheng TingLuo LimanWang XingDeng XuanXue Mei - Despite being recognized as a critical oncogenic survival factor across multiple malignancies, the functional role and regulatory architecture of Fetal and Adult Testis Expressed 1 (FATE1) in breast cancer (BC) remain mechanistically obscure. Through integrated online database analysis and validation study, we demonstrate that FATE1 exhibits significant tumor-specific overexpression in BC, correlating with adverse clinical outcomes (HR [hazard ratio] = 2.017, 95 %CI: 1.052-3.869, P = 0.0165) in a 129-patient BC cohort. Functional characterization revealed FATE1 overexpression potentiates proliferative, migratory, and invasive capacities in MCF-7 cells, concomitant with accelerated autophagic flux evidenced by p62 degradation and enhanced LC3-I/II conversion. Genetic ablation of FATE1 in MDA-MB-231 cells reciprocally attenuated these oncogenic phenotypes. Mechanistically, FATE1 orchestrates JAK2/STAT1 pathway activation through upregulation of both JAK2 and STAT1, with concomitant phosphorylation increases. Pharmacological inhibition with JAK-IN-23 (C23H22Cl2N4O, a specific JAK/STAT inhibitor) abrogated FATE1-mediated oncogenicity and autophagic activity. This work establishes FATE1 as a novel prognostic biomarker and therapeutic target in BC, delineating its oncogenic role in tumor progression through JAK2/STAT1 pathway-mediated proliferation and autophagy regulation. - Source: PubMed
Publication date: 2025/07/12
Xie YanFu RuiminXiao ZhengLi Gang - Cellular metabolism is a key regulator of cell fate, raising the possibility that the recently discovered metabolic heterogeneity between newly synthesized and chronologically old organelles may affect stem cell fate in tissues. In the small intestine, intestinal stem cells (ISCs) produce metabolically distinct progeny, including their Paneth cell (PC) niche. Here we show that asymmetric cell division of mouse ISCs generates a subset enriched for old mitochondria (ISC), which are metabolically distinct, and form organoids independently of niche because of their ability to recreate the PC niche. ISC mitochondria produce more α-ketoglutarate, driving ten-eleven translocation-mediated epigenetic changes that promote PC formation. In vivo α-ketoglutarate supplementation enhanced PC turnover and niche renewal, aiding recovery from chemotherapy-induced damage in aged mice. Our results reveal a subpopulation of ISCs whose old mitochondria metabolically regulate cell fate, and provide proof of principle for metabolically promoted replacement of specific aged cell types in vivo. - Source: PubMed
Publication date: 2025/07/14
Andersson SimonBui HienViitanen ArtoBorshagovski DanielSalminen EllaKilpinen SamiGebhart AngelikaKuuluvainen EmiliaGopalakrishnan SwethaPeltokangas NinaJames MartynAchim KaiaJokitalo EijaAuvinen PetriHietakangas VilleKatajisto Pekka