Ask about this productRelated genes to: TRADD Blocking Peptide
- Gene:
- TRADD NIH gene
- Name:
- TNFRSF1A associated via death domain
- Previous symbol:
- -
- Synonyms:
- Hs.89862
- Chromosome:
- 16q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-07
- Date modifiied:
- 2016-10-05
Related products to: TRADD Blocking Peptide
Related articles to: TRADD Blocking Peptide
- Pancreatic cancer is one of the most lethal malignancies worldwide, characterized by late diagnosis, aggressive progression, and poor survival. Dysregulation of regulated cell death (RCD) pathways, including apoptosis, ferroptosis, necroptosis, and mitochondrial dysfunction, contributes to tumor survival, therapy resistance, and immune evasion. Understanding the molecular mechanisms underlying these processes is critical for identifying prognostic biomarkers and therapeutic targets. Publicly available pancreatic cancer gene expression datasets (GSE227567 and GSE275246) were analyzed to identify differentially expressed RCD and mitochondrial genes. FRGs, APGs, NRGs, and MGs were intersected with the DEGs, followed by functional enrichment, protein-protein interaction (PPI) network construction, and hub gene prioritization. Co-expression, immune infiltration, and pathway activity analyses were performed across pathological stages and pan-cancer datasets. Missense SNPs in top hub genes ATF4 and PMAIP1 were evaluated for structural and energetic impact using HOPE and DynaMut. Analysis identified 448 FRGs, 73 APGs, 32 NRGs, and 930 MGs in GSE227567, and 123 APGs, 0 FRGs, 36 NRGs, and 577 MGs in GSE275246. Cross-dataset overlap was highest for APGs (116 genes), while other RCD and mitochondrial genes were largely dataset-specific. Filtering and PPI network analysis prioritized nine hub genes (ATF4, PMAIP1, BCL2L1, ATF3, TRADD, SRC, SFN, KCNMA1, GUK1). Functional enrichment highlighted mitochondrial metabolism, oxidative phosphorylation, and apoptosis pathways, with integration into PI3K-AKT, MAPK, p53, and VEGF signaling. Immune infiltration analysis revealed myeloid-enriched tumor microenvironments in mutant contexts. Pan-cancer and stage-wise expression profiling indicated that ATF4 and PMAIP1 exhibit consistent stage-dependent modulation. Survival analysis showed that high PMAIP1 expression correlates with poor prognosis (HR = 1.26, p = 0.00185), while ATF4 shows a protective trend (HR = 0.84, p = 0.0145). SNP analysis revealed six missense variants in each gene, with ATF4 variants predominantly destabilizing and affecting the bZIP domain, whereas PMAIP1 variants were mostly surface-exposed and modulatory. Our integrative analysis identifies ATF4 and PMAIP1 as key RCD- and mitochondrial-associated genes in pancreatic cancer, with functional SNPs that influence prognosis and may serve as therapeutic targets. These findings provide insights into mitochondrial-driven apoptosis, tumor progression, and potential avenues for precision medicine interventions. - Source: PubMed
Publication date: 2026/04/23
Ali Syed LuqmanAli AwaisKhatrawi Elham MohammedKiran RafiaKhan Bilal - Extensive research continues to address the challenges of developing standard cancer drugs. However, until more effective standard drugs are developed, ferulic acid (FA) may be a potential option for controlling the symptoms of cancer patients. According to our review, FA is available in natural sources and has flexible structures that possess diverse pharmacological activities. FA is effective against 16 different cancer types and has been validated in cell culture, preclinical, and clinical models. Chemotherapeutics activities of FA are regulated through varieties of mechanisms, including targeting signaling pathways, such as AKT/PI3K/mTOR/ERK/STAT NF-κB; apoptosis, such as FAS/FASL, TRADD, Bcl2, Bax, Caspases, and PARP; metastasis, such as MMPs(1,2,9), Wnt/-β catenin, angiogenesis (E&N Cadherin, vimentin, Snail, and Slug), cell proliferation (cyclin D1, E1, and CDKs(2,4,6)), inflammatory molecules (TNF-α, NF-κB,1α, IL-10, IL-8, and IL-6), regulating tumor suppressor genes (p-RB, p21, and p53), autophagy (LC3-II, p62, Beclin1, and Atg12-Atg5), glycolysis (lncRNA 495810 and PKM2), heat shock protein (Hsp60, Hsp70, and Hsp90), and some nonspecific pathways, such as oncogene suppression and antioxidant efficacies. Nanoformulation of FA increased its solubility, stability, and bioavailability, thereby enabling controlled release and making FA more effective against cancer. Additionally, FA exerted synergistic effects with other natural compounds, vitamins, radiotherapy, and chemotherapies, and reversed resistance to existing chemotherapies via diverse mechanisms, including targeting multidrug resistance proteins, apoptosis, reactive oxygen species production, hypoxia, microRNA, the β-catenin pathway, oncogene activation, and sensitizing chemotherapies and radiotherapies. Given that FA has validated the experimental model and demonstrated preliminary efficacy, these findings suggest a possible supportive role for phytochemicals pending the development of fully effective pharmaceutical therapies. - Source: PubMed
Publication date: 2026/04/20
Khatun SanzidaSohel MdBarman ZituSalma UmmeArbia LubatulSarker Md RifatJame Jasmin AkterDey Badhan RaniParvin SultanaShuvo Md Shah PoranIslam Md ShahidulMannan TaniaDas Snygdha RaniHasan Md Mahmudul - 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 - This study aims to explore the mechanism of Shuangshen Yiwei Granules, an empirical prescription developed by Professor LU Zhi-zheng(a master of TCM), in regulating gastric acid secretion and impeding malignant progression of chronic atrophic gastritis with gastric intestinal metaplasia(GIM). Seventy-two specific-pathogen free(SPF) Wistar male rats were randomly divided into a normal group and a modeling group. GIM model rats were established by a four-factor GIM induction protocol involving "N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), ranitidine, irregular feeding, and sodium salicylate". After successful modeling, the rats in the modeling group were further divided into a model group, a positive control(Moluodan), and a Shuangshen Yiwei Granules group, with 12 rats in each group. Each group was continuously intervened for eight weeks. General conditions were observed, and pathological changes in the gastric mucosa were evaluated via hematoxylin-eosin staining. Serum pepsinogen Ⅰ(PGⅠ), pepsinogen Ⅱ(PGⅡ), and gastrin-17(G-17) were quantified by enzyme-linked immunosorbent assay. Parietal cell ultrastructure was analyzed via transmission electron microscopy. The apoptosis of gastric glandular cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining. Gastric pH was measured with precision test strips. The expression of apoptosis pathway-related proteins Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) and tumor necrosis factor receptor 1(TNFR1)/cysteine-aspartic acid protease-8(caspase-8) and acid secretion-related proteins cyclin dependent kinase 5(CDK5)/soluble N-ethylmaleimide sensitive factor attachment protein receptors(SNAREs) in gastric mucosal tissue were detected by Western blot. Compared to the normal group, the model group exhibited lethargy in mental state, pale eyes/ears/claws/tongue, tail desquamation, glandular atrophy of the gastric mucosa with disordered arrangement, and tumor-like structures, significantly reduced PGⅠ, PGⅠ/PGⅡ ratio, and G-17(P<0.01), significantly elevated PGⅡ(P<0.01), parietal cell nuclear condensation, loss and abnormal structures of mitochondria, significantly increased gastric glandular apoptosis(P<0.01), and significantly elevated gastric pH(P<0.01). The levels of p-JAK2/JAK2, p-STAT3/STAT3, B-cell lymphoma-2(Bcl-2)-associated X protein(Bax)/Bcl-2, TNFR1, TNFR1 associated via death domain(TRADD), Fas-associated death domain(FADD), and cleaved caspase-8/caspase-8 significantly increased(P<0.05, P<0.01), while histamine receptor H_2(HRH_2), CDK5, syntaxin 3(STX3), and synaptosome associated protein 25(SNAP25) significantly decreased(P<0.05). Compared with the model group, the Shuangshen Yiwei Granules group exhibited alleviated mental state, general conditions, and pathological features of the gastric mucosa, significantly upregulated PGⅠ, PGⅠ/PGⅡ ratio, and G-17(P<0.05, P<0.01), significantly downregulated PGⅡ(P<0.01), ameliorated parietal cell ultrastructure to varying degrees, significantly reduced gastric glandular apoptosis(P<0.01), significantly lowered gastric pH(P<0.01), significantly decreased expression of p-JAK2/JAK2, p-STAT3/STAT3, Bax/Bcl-2, TNFR1, TRADD, FADD, and cleaved caspase-8/caspase-8(P<0.05, P<0.01), and significantly increased expression of HRH_2, CDK5, STX3, and SNAP25(P<0.05). To sum up, Shuangshen Yiwei Granules potentially inhibit JAK2/STAT3 and TNFR1/caspase-8 signaling pathways to suppress gastric glandular apoptosis while activating CDK5/SNAREs to enhance parietal cell acid secretion, thereby restoring gastric acid homeostasis and blocking GIM progression. - Source: PubMed
Wang Yan-MinYu Yu-LingWang Si-QiSun Ya-TengYan Yong-HuangYang Xin-YuHan Si-QiSong Yu-HongWang Yu-HanWang Yun-HeZhang CaiSu Ze-Qi - SARS-CoV-2 infection-induced syncytia formation accelerates cell-to-cell transmission of the virus and enhances viral evasion by neutralizing antibodies. Host innate immune response plays a key role in controlling viral infection. Our present work identifies tumor necrosis factor (TNF) as a key cytokine quickly released from activated innate immune cells that suppresses SARS-CoV-2 spike-mediated cell-cell fusion. Mechanistically, TNF signals through the TNFR1-TRADD/TRAF2/RIPK1-MAPK-SDC4 axis. SDC4 further activates the RhoA/ROCK signaling pathway, which promotes cytoskeletal reorganization, leading to the formation of actin bundles at the interface between infected cell and adjacent cell. Such remodeling of actin effectively blocks further propagation of syncytia and viral spreading. These findings provide critical insights into the dynamic interplay between host antiviral factors and syncytia formation, deepening our understanding of the innate immune control of SARS-CoV-2 infection. - Source: PubMed
Publication date: 2026/02/14
Duan DongZheng XuZhou YanqiuCui MengmengLi YunyiCui XiaoxianYang YuyingChen MinWu HuanyuChen XinMeng Guangxun