Ask about this productRelated genes to: TFDP1 Blocking Peptide
- Gene:
- TFDP1 NIH gene
- Name:
- transcription factor Dp-1
- Previous symbol:
- -
- Synonyms:
- Dp-1, DRTF1, DP1, DILC
- Chromosome:
- 13q34
- Locus Type:
- gene with protein product
- Date approved:
- 1995-02-02
- Date modifiied:
- 2016-01-29
Related products to: TFDP1 Blocking Peptide
Related articles to: TFDP1 Blocking Peptide
- Cisplatin-based combination therapy remains the primary treatment modality for patients with advanced bladder cancer (BCa); however, the emergence of drug resistance severely restricts clinical benefits. The molecular mechanisms underlying chemoresistance remain incompletely understood. By integrating single-cell transcriptomics with in vitro and in vivo experiments, we revealed that cholesterol metabolism was significantly hyperactivated in cisplatin-resistant BCa tissues. Further subpopulation re-clustering identified a specific chemoresistant epithelial cell subset (C3) characterized by robust cholesterol metabolism, in which the cholesterol metabolic enzyme DHCR24 was significantly upregulated and played a pivotal role in mediating cisplatin resistance in BCa. Mechanistically, the elevated expression of TFDP1 in cisplatin-resistant BCa epithelial cells upregulated DHCR24 via the formation of the TFDP1-E2F1 transcriptional complex, thereby promoting cholesterol biosynthesis. The enriched intracellular cholesterol facilitated the formation of cell membrane lipid rafts and enhanced the phosphorylation of Src, which in turn hyperactivated the downstream MAPK signaling pathway, ultimately conferring cisplatin resistance. Furthermore, the accumulated cholesterol enhanced PD-L1 protein stability, thereby impairing the efficacy of immunotherapy in BCa. Taken together, our study characterizes a specific DHCR24+ tumor epithelial subpopulation that orchestrates cisplatin resistance via the "cholesterol-lipid raft-MAPK" axis. These findings establish a clear mechanistic link between cholesterol metabolism and cisplatin sensitivity. - Source: PubMed
Publication date: 2026/08/29
Zhao YuanqiaoXing ZhuoWang MengmengFu LiangminLiu RuilinDing ZexianLi YuanWang YinhuaiYan BinZhu Xueqiang - Sepsis frequently leaves patients with persistent immune impairment that contributes to late mortality, yet the anatomical routes that transmit this response to the lung remain poorly defined. Here, we identify the spleen as a key extramedullary hub orchestrating pulmonary immune paralysis through a spleen-lung axis. Mechanistically, splenic programmed death-ligand 1 (PD-L1) polymorphonuclear myeloid-derived suppressor cells undergo TFDP1-driven expansion and migrate to the lungs via CXCL2/CXCR2 signaling, establishing an interorgan immunosuppressive circuit. In the lung, these cells reprogram alveolar macrophages through programmed death-1 (PD-1)-dependent checkpoint signaling, inducing a dysfunctional state characterized by impaired antibacterial responses and enrichment of complement and immune checkpoint pathways. Genetic or pharmacologic disruption of the PD-L1-PD-1 axis restores macrophage function and improves pulmonary host defense in experimental sepsis. Together, these findings define a mechanistic link between splenic myelopoiesis and distal lung immune paralysis. - Source: PubMed
Publication date: 2026/08/19
Xie BingHan MengqiWen XiaoyueYuan YinQi HongZhang YujingWang XinZhen ZifanWang MengyuanZhang XinyuJin TingtingSun XueqiangWang ZhigangLi XiaofengYuan ShiyingZhang JianchengShang You - Triple-negative breast cancer is marked by extensive cellular heterogeneity and limited availability of actionable targeted treatments, which contributes to an unfavorable prognosis. In this work, single-cell and spatial transcriptomic profiling was integrated with network-based analyses and machine-learning approaches to characterize malignant epithelial programs in TNBC and to pinpoint prognostic biomarkers.Single-cell RNA sequencing identified a malignant epithelial subpopulation, Luminal_inflam, characterized by elevated inferred copy number variation, a terminal pseudotime state, and enrichment of cell cycle-associated transcriptional programs. Cell-cell communication analysis indicated microenvironmental remodeling in TNBC and prioritized a fibroblast-associated S100A4-EGFR axis that may regulate Luminal_inflam-associated gene expression. Gene regulatory network analysis further revealed increased activities of transcription factors including MYBL2, TFDP1, CEBPD, and MBD2. A 12-gene risk signature constructed from Luminal_inflam-associated modules and survival cohorts effectively stratified overall survival and captured differences in immune features and potential drug sensitivities. In our MDA-MB-231 model, RPN1 knockdown was associated with reduced cell viability, which could be partially rescued by 4-PBA. We further found that RPN1 depletion was accompanied by increased intracellular ROS and Ca levels, altered cell-cycle distribution, and elevated apoptosis, and that these changes were also partially reversible upon 4-PBA treatment. These data support the view that loss of RPN1 perturbs ER homeostasis and is linked to stress-associated cell fate changes in TNBC cells. At the same time, these findings should be interpreted in the context of prior work showing that RPN1 depletion can induce ER-stress-dependent apoptosis in breast cancer models. Thus, rather than establishing an entirely new mechanism, our study extends previous observations by connecting this stress-related phenotype to a specific malignant epithelial program and a clinically derived risk framework.Collectively, this study delineates a key malignant epithelial state in TNBC and suggests that RPN1-associated proteostasis vulnerability may represent a potential therapeutic opportunity. - Source: PubMed
Publication date: 2026/06/11
Wu JinpengFan JingjingSha TongLi Hongtao - Inflammatory bowel disease (IBD) is characterized by dysregulated T cell responses. RNA helicases, including DExD-box helicase 21 (DDX21), are pivotal in RNA metabolism, but their role in T cell-mediated pathology during IBD remains unclear. Here, we demonstrate that DDX21 expression in CD4 T cells correlates with cell cycle and translation pathways in IBD-affected tissues. Conditional deletion of Ddx21 in mouse T cells disrupts T cell homeostasis and impairs cell proliferation. Consequently, Ddx21-deficient CD4 T cells exhibit resistance to inducing adoptive transfer colitis, with recipients showing reduced T cell infiltration compared to wild-type (WT) counterparts. Mechanistically, DDX21 ensures ribosome biogenesis after T cell activation and facilitates mRNA translation of Transcription factor dp-1 (TFDP1), a transcription factor critical for cell cycle progression. Given this dependence on ribosome biogenesis, pharmacological targeting of this pathway via KU55933-an inhibitor of ribosome synthesis-related signaling-recapitulated the protective effects of DDX21 loss: KU55933 alleviated dextran sulfate sodium (DSS)-induced colitis in mice and attenuated pathogenic CD4 T cell expansion. Our findings establish DDX21 as a key regulator of T cell proliferation and highlight its potential as a therapeutic target for IBD and other autoimmune disorders. - Source: PubMed
Publication date: 2026/05/29
Zhang YujuanKan ChenYang XinhuiHao YajuanCai XueminYang MeiZhang QianqianWang ZhengtingJiang NingWang LeiLi Hua-BingZhou Jing - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease influenced by multiple genetic and environmental factors.. This study used bioinformatics to identify new diagnostic biomarkers and explore the pathogenesis of SLE. - Source: PubMed
Publication date: 2026/05/11
Pan QingboYu XuliangZhu JinZheng Xiaojin