Ask about this productRelated genes to: DHX15 Blocking Peptide
- Gene:
- DHX15 NIH gene
- Name:
- DEAH-box helicase 15
- Previous symbol:
- DDX15
- Synonyms:
- HRH2, DBP1, PRP43, PrPp43p, PRPF43
- Chromosome:
- 4p15.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-12-05
- Date modifiied:
- 2016-10-05
Related products to: DHX15 Blocking Peptide
Related articles to: DHX15 Blocking Peptide
- Methylchloroisothiazolinone (CMIT) and polyhexamethylene guanidine (PHMG) are antimicrobial biocides associated with pulmonary toxicity, although their comparative cellular stress mechanisms remain unclear. Here, we investigated how CMIT and PHMG differentially alter the proteome of human alveolar epithelial A549 cells under subcytotoxic conditions. Cells were exposed to CMIT or PHMG, and global proteomic profiling was performed using label-free liquid chromatography-tandem mass spectrometry. Differentially expressed proteins (DEPs) were identified at a 1% false discovery rate with an absolute log2 fold change ≥1. Functional analyses were conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis, and selected proteins were validated by western blotting. Comparative toxicoproteomics revealed distinct stress-response signatures induced by the two biocides. CMIT preferentially altered proteins associated with proteostasis, oxidative stress, and protein quality control, whereas PHMG was characterized by coordinated depletion of ribosome-associated and translation-related proteins. A total of 73 and 155 DEPs were identified in CMIT- and PHMG-treated cells, respectively, with 22 proteins shared between treatments. Western blotting confirmed PSMD3, TUBB2A, and GLRX1 as CMIT-responsive proteins and THRAP3, DHX15, and RPL4 as PHMG-responsive markers. These findings provide comparative mechanistic insight into how CMIT and PHMG induce distinct epithelial stress responses and identify candidate protein markers that may support future in vitro assessment of biocide-induced pulmonary toxicity. - Source: PubMed
Publication date: 2026/09/06
Jeong Ye-EunJeon Min JeongYoun Hyung-SunHan JiyouLee Mi-Young - The RUNX1::RUNX1T1 translocation, also termed AML1-ETO, is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML) and is associated with variable clinical outcomes. The R222G hotspot mutation, located in the RNA helicase gene DHX15, is enriched and predominantly found in AML with this translocation, but its diagnostic significance and underlying mechanism remain largely unclear. In this study, we show that pediatric AML patients carrying DHX15 mutations exhibit an inferior prognosis. Functional analysis demonstrates that DHX15 cooperates with AML1-ETO fusion protein to enhance AML leukemia stem cell (LSC) activity and promote resistance to standard chemotherapy. Mechanistically, AML1-ETO transcriptionally upregulates mitochondrial transcription factor A (TFAM), while DHX15 promotes TFAM protein stabilization and nuclear translocation, resulting in robust activation of oxidative phosphorylation (OXPHOS) gene expression and mitochondrial respiration. Inhibition of oxidative phosphorylation by the Complex V inhibitor S-Gboxin exerts strong anti-leukemic effects and efficiently circumvents chemotherapy resistance in AML1-ETO DHX15 leukemia. These findings underscore the pivotal role of oncogenic DHX15 mutations in regulating AML LSC activity and identify DHX15 as a potential genetic biomarker for AML risk stratification. Moreover, this mutation may predict therapeutic vulnerability to OXPHOS inhibition. - Source: PubMed
Publication date: 2026/08/21
Li QilongXing PeiqiXu JinLi JifeiChen LiangjieLi XinluBai YinpengLi GangXie TingWang LuzhenWang YuanQing GuoliangWang HuafengShao LiangWu WeiLiu ZhaoqiLiu Hudan - The innate immune response is a first line of defense that allows a rapid reaction to pathogens as well as molecules released from damaged cells. It relies on pathogen-sensing receptors, many of which are nucleic acid-binding proteins, including RNA helicases. Plakophilin 1 (PKP1) is a desmosomal protein essential for strong intercellular adhesion and epithelial barrier integrity. Loss-of-function mutations in PKP1 cause ectodermal dysplasia-skin fragility syndrome (EDSFS), which is characterized by skin fragility, chronic inflammation, and recurrent infections. Here, we report that PKP1, whose role in barrier formation is to function as a critical regulator of innate immune responses. PKP1 sequesters a subset of dsRNAs that sense DExD/H-box RNA helicases-DDX1, DDX3X, DDX21, and DHX15. This limits their ability to activate the MDA5-MAVS signaling axis and prevents excessive activation of IRF3- and NFκB-driven gene expression, including the synthesis of proinflammatory cytokines, mainly IFN-β1, IL6, and TNFα. The inhibitory role of PKP1 is erased during innate immune responses by dsRNA cues, inducing proteasomal PKP1 degradation. This releases sequestered helicases, enabling dsRNA sensing and a rapid inflammatory response. Collectively, these findings identify PKP1 as a key gatekeeper that prevents exaggerated inflammation in quiescent keratinocytes, which is supported by excessive inflammation in EDSFS upon PKP1 loss. In healthy keratinocytes with proinflammatory traits, PKP1 is rapidly degraded, allowing the activation of the MDA5-MAVS signaling cascade by helicases to initiate inflammation. Hence, PKP1 combines two complementary functions essential for epidermal immune homeostasis: it provides a physical barrier preventing substance entry and suppresses innate immune responses in keratinocytes. - Source: PubMed
Publication date: 2026/08/19
Keil RenéMisiak DannyHüttelmaier StefanTellkamp FrederikKrüger MarcusHatzfeld Mechthild - Breast cancer (BC) is a disease that occurs relatively frequently, and its prognosis and treatment outcomes are not optimal at present. Identifying novel BC biomarkers and therapeutic targets is key. DEAH-box helicase 15 (DHX15) is an RNA helicase that exhibits enhanced activity and is closely associated with tumorigenic potential. Alternative splicing is widely dysregulated in BC. However, the biological function of DHX15 in BC, in addition to its underlying molecular mechanisms, remain unclear. DHX15, a key RNA helicase involved in splicing regulation, was therefore selected to explore whether it modulates the malignant progression of BC. The present study therefore analyzed the DHX15 expression profile in BC using the Tumor Immune Estimation Resource database. Kaplan-Meier plotter database was utilized to investigate the prognostic value of DHX15 in BC. The Cancer Genome Atlas-BRCA database was utilized to investigate the association between DHX15 and immune infiltration, as well as the expression of immune biomarkers, within the tumor microenvironment. The potential biological functions of DHX15 in BC were also investigated using Gene Ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes pathway analysis (KEGG) and single-cell functional analysis. GO and KEGG enrichment analyses were performed via the GSEA module embedded in the LinkedOmics database. Single-cell functional analysis was performed using the Human Proteome Atlas database and the CancerSEA database. Concurrently, the expression and function of DHX15 in BC was validated. MDA-MB-231 cells were transfected with a DHX15 knockdown plasmid and MCF-7 cells with an overexpression plasmid, and Transwell assays, plate cloning and scratch assays were performed on the established cell lines. The present findings revealed that the DHX15 expression levels in BC were notably higher compared with those in normal tissues. Furthermore, the expression of DHX15 was associated with immune checkpoints (such as PDCD1, LAG3 and GZMB) and immune cell infiltration (such as T helper cells and central memory T cells) in BC, as determined by single-sample Gene Set Enrichment Analysis and CIBERSORT analyses. experiments suggested that inhibiting DHX15 notably suppressed the migration, invasion and proliferation of MDA-MB-231 cells. Collectively, these findings suggest that the high expression of DHX15 in BC is associated with worse prognosis and immune cell infiltration, potentially by functionally promoting tumor cell proliferation, migration and invasion. - Source: PubMed
Publication date: 2026/08/05
Li FanYue QinLi Jing - The AML1-ETO (AE) fusion gene, resulting from t(8;21)(q22;q22), represents a prevalent subtype of acute myeloid leukaemia (AML). Retention of exon 9a between exon 8 and 9 of the ETO (RUNX1 Partner Transcriptional Co-Repressor 1, also name RUNX1T1) gene generates the oncogenic AML1-ETO9a (AE9a) splice variant. Here, we uncover the potential involvement of RNA (ribonucleic acid) helicase DHX15 (DEAH-box helicase 15) in AE9a splicing and AML progression. Clinically, higher expressed DHX15 is associated with increased AE9a/AE abundance and poor outcomes in AE-positive (AE) AML patients. DHX15 knockdown impaired cell proliferation, induced S/G2 cell-cycle arrest in vitro and prolonged overall survival in AE leukaemia-bearing mice in vivo. In addition, DHX15 knockdown reduced AE and AE9a expression, and RNA immunoprecipitation revealed DHX15 bound to AE and AE9a transcripts and RNA pull-down assay showed a selective interaction of HNRNPL and RBM33 with AE9a transcripts. Three-dimensional structure prediction suggests a sophisticated regulatory complex formation involving DHX15, HNRNPL (heterogeneous nuclear ribonucleoprotein L) and RBM33 (RNA binding motif protein 33). Further, HNRNPL and RBM33 gene expression positively correlated with AE9a levels in AE AML samples. Downregulation of HNRNPL and RBM33 reduced AE9a expression in Kasumi-1 cells. Collectively, our findings support an association between DHX15, HNRNPL, RBM33 and AE9a splicing and suggest their contribution to leukemogenic progression in AE AML. - Source: PubMed
Publication date: 2026/07/12
Liu QiaoWang XuechunFan JiqiangZheng YiYe LuyaChang WenhanChen XiangleiCai YuanhuaLai XiaolinLi YangPan LiliLi XiaofanLin RenJangWang Shaoyuan