Ask about this productRelated genes to: DDX3X Blocking Peptide
- Gene:
- DDX3X NIH gene
- Name:
- DEAD-box helicase 3 X-linked
- Previous symbol:
- DDX3
- Synonyms:
- DBX, HLP2, DDX14
- Chromosome:
- Xp11.4
- Locus Type:
- gene with protein product
- Date approved:
- 1998-04-29
- Date modifiied:
- 2018-04-26
Related products to: DDX3X Blocking Peptide
Related articles to: DDX3X Blocking Peptide
- The loss of chromosome Y (LOY) in leukocytes is the most prevalent form of clonal mosaicism observed in older men. Previous studies provided multiple pieces of evidence for the effect of LOY on the immune system and connected LOY to elevated risk of all major causes of mortality, including cardiovascular diseases and cancer. Despite these associations, the dynamic effects of LOY across the developmental trajectories of immune cell populations remain unclear. We utilized single-cell RNA-sequencing data from the peripheral blood mononuclear cells of 416 male donors (median age = 68) from the OneK1K cohort. LOY was identified in 45,304 cells (8.76%) and exhibited cell type-specific effects on immune cells along the differentiation trajectories. The largest frequency was detected in monocytes (18.6% in classical and 17.1% in nonclassical) with a progressive decrease along the transition trajectory from 22.6% to 15.8% (p = 2.00 × 10), and a gradual reduction in the expression of nonclassical markers LYPD2 and C1QA. LOY is associated with a profibrotic signature in classical monocytes marked by downregulation of IL1B (log FC = -0.22, p = 2.84 × 10) and MYC-regulated genes (log FC = -0.25, p = 2.22 × 10), consistent with previous observations that LOY-associated macrophages are polarized toward a fibrotic rather than inflammatory phenotype in cardiac and pulmonary injury. Notably, we detected aberrant expression of XIST, the essential X-chromosome-inactivation lncRNA that is not normally expressed in males, and upregulation of genes known to escape X-inactivation, including male-biased cancer-related genes KDM6A, DDX3X, KDM5C, and ZRSR2. Our results indicate associations between LOY and cell type-specific transcriptional changes, including aberrant X-inactivation features. - Source: PubMed
Dawoud AhmedGreen LukeRackham Owen - DDX3X is a multifunctional DEAD-box RNA helicase with important roles in translation initiation and antiviral innate immune signaling, yet it is currently unknown whether viral infection affects its interactions with host RNAs. Here, we define the transcriptome-wide binding landscape of endogenous DDX3X in Sendai virus-infected human cells using PAR-CLIP. We show that DDX3X maintains its preference for GC-rich, highly structured 5'UTR regions during infection, but acquires a distinct set of infection-induced targets, including and multiple interferon-stimulated genes. We demonstrate that DDX3X directly binds the 5'UTR and promotes its translation, establishing a previously unrecognized post-transcriptional mechanism contributing to DDX3X-dependent IFN-β production. We also evaluated DDX3X's binding to SeV RNAs and concluded that DDX3X is likely not actively recruited by SeV or has a significant effect on its viral life cycle. Our findings add a novel dimension to DDX3X's involvement in anti-viral immunity with implications for further therapeutic development of DDX3X inhibitors. - Source: PubMed
Publication date: 2026/03/09
Ryan Cathal SAnastasakis Dimitrios GPolash Ahsan HSitko ElizabethHafner MarkusSchröder Martina - Sex differences influence congenital heart disease (CHD) development, yet underlying molecular mechanisms remain largely unclear. We demonstrate that the X-linked RNA helicase DDX3X associates in the heart with ribosomal subunit proteins, and eCLIP mapping reveals its preferential binding to cardiac mRNAs with long, structured 5' untranslated regions (UTRs) that can hinder translation. Using a cardiomyocyte-specific mouse knockout model, we show that female embryos lacking die at midgestation from heart failure due to impaired translation of key cardiac regulators, whereas male littermates survive. Ribosome profiling and proteomics demonstrate that DDX3X is required for efficient translation of female differential cardiac mRNAs. Reporter assays confirm that translation of essential cardiac genes such as and depends on their 5' UTRs and requires DDX3X. These findings uncover a sex-specific posttranscriptional mechanism by which DDX3X safeguards female heart development through selective mRNA translation, providing insight into how X-linked dosage-sensitive regulators contribute to CHD. - Source: PubMed
Publication date: 2026/04/27
Mason Kayla KPark Seohyun KEmerson James ILu Yao WeiWang Da-ZhiMarzluff William FConlon Frank L - Aseptic loosening (AL) represents the primary cause of joint arthroplasty failure, which is predominantly triggered by chronic inflammatory reactions to prosthetic wear particles, with macrophages serving as the central effector cells. Accumulating evidence indicates that the crosstalk between endoplasmic reticulum stress and mitochondrial stress exacerbates macrophage-mediated inflammation; however, the core molecular regulators orchestrating this pathological cascade remain elusive. Herein, we investigated the functional role of the GATA6/DDX3X (DEAD-box helicase 3 X-linked) axis in titanium particle (TiP)-induced macrophage inflammatory responses and further explored the therapeutic potential of nanoparticle-loaded injectable hydrogels for AL. Specifically, a si-DDX3X-loaded nanoparticle hydrogel (si-DDX3X NPs@Hy) was fabricated and characterized, and its therapeutic efficacy was evaluated in vivo. Our results demonstrated that DDX3X expression was significantly up-regulated in both TiP-stimulated bone marrow-derived macrophages and periprosthetic tissues obtained from AL patients. Functional assays revealed that DDX3X promoted mitochondria-endoplasmic reticulum interplay, which in turn facilitated NLRP3 inflammasome assembly and subsequent interleukin-1β secretion. Mechanistically, GATA6 directly bound to the transcription start site of the DDX3X gene, thereby suppressing its transcriptional expression and abrogating DDX3X-mediated proinflammatory effects. The synthesized si-DDX3X NPs@Hy exhibited favorable physicochemical properties; local administration of this hydrogel markedly attenuated TiP-induced calvarial osteolysis in mice, accompanied by reduced osteoclastogenesis, proinflammatory cytokine production, and M1 macrophage polarization in the lesion microenvironment. Collectively, this study identifies the GATA6/DDX3X axis as a pivotal regulator of TiP-driven macrophage inflammation and validates the si-DDX3X NPs@Hy as a promising therapeutic strategy for targeting wear particle-induced inflammation, which holds great potential for improving the long-term prognosis of joint arthroplasty. - Source: PubMed
Publication date: 2026/04/16
Lin SipengLiu TaiheZhu QiOuyang ZhujiYu YifanSun HaopengLi ChangchuanLi ShixunPan ChenhaoKo Wing CheukLiu HaoxianLiu JinLi ShuangxingChen JinchangWu ShaojianYe JichaoGao LiangbinDing Yue - Baicalein, a naturally occurring flavonoid with well-documented anti-inflammatory and neuroprotective effects, has shown therapeutic promise in multiple models of neurological disorders. However, whether baicalein can counteract diquat-induced neurotoxicity remains uncertain. This study reveals that baicalein alleviates diquat-induced neuroinflammation and microglial pyroptosis in mice in a gut microbiota (GM)-dependent manner. In the in vivo experiments, multi-omics analyses demonstrated that baicalein elevates the GM-derived metabolite indole-3-propionic acid (IPA), which was sufficient to suppress pyroptosis. In parallel, IPA was identified as a critical mediator of baicalein's neuroprotective effects, as exogenous IPA administration recapitulated baicalein's protection, and baicalein treatment significantly elevated IPA levels. Mechanistically, through inhibiting the DEAD-box helicase 3 X-linked / GTPase-activating protein (SH3 domain) binding protein 1 pathway by in vitro experiments. Our study demonstrated that baicalein mitigates diquat-induced neuroinflammation, underscoring the therapeutic potential of targeting the GM to counteract herbicide-related neurotoxicity. - Source: PubMed
Publication date: 2026/04/10
Li TingFeng MengxiaoWang PingJiang MiaoCui JaiyuJin MengxiaSong CongyingLin LiyingLu Yuan-Qiang