Ask about this productRelated genes to: DHX8 Blocking Peptide
- Gene:
- DHX8 NIH gene
- Name:
- DEAH-box helicase 8
- Previous symbol:
- DDX8
- Synonyms:
- HRH1, PRP22, PRPF22, Dhr2
- Chromosome:
- 17q21.31
- Locus Type:
- gene with protein product
- Date approved:
- 1995-12-20
- Date modifiied:
- 2017-05-26
Related products to: DHX8 Blocking Peptide
Related articles to: DHX8 Blocking Peptide
- Human DHX8 is a spliceosomal DEAH-box RNA helicase involved in releasing mRNA from the spliceosome and crucial in ensuring splicing fidelity. DHX8 was identified as a promising therapeutic oncology target due to its role in regulating stress-adaptive gene expression, including HSF1-dependent transcription, while having broader transcriptional effects in cells under oncogenic stress. We report the discovery of novel RNA-competitive DHX8 inhibitors based on a 2-(phenethylthio)nicotinic acid scaffold, which were optimized using a structure-guided design approach, following a biophysical fragment screen. This yielded compound 53 with nanomolar biochemical potency, good in vitro PK, and activity in a cellular target engagement assay. Optimizing inhibitor binding between Arg647 and the nonconserved His693, coupled with extending into a pocket in the DHX8 Winged-Helix domain, was crucial for potency improvement. By binding in the Winged-Helix domain, these inhibitors restrict the helicase domain's conformational plasticity, stabilizing a closed, inactive conformation while sterically blocking ssRNA translocation. - Source: PubMed
Read Benjamin JEwens CarolineGigante FedericaThomas JemimaFelisberto-Rodrigues CatarinaAlvarez Peres SilviaTighe Catherinede Las Heras Ruiz EdgarSchiemann KaiMalcolm Andrew GMcAndrew Peter CraigStubbs MarkPatani HarshniraCosta Helena Dos SantosStoodley KatharinePickard LisaBusch MichaelGunnell EmmaSilva SaraKnopp AlexandraHallett Stephen TAugustin MartinLammens AlfredCarter MichaelMeniconi MircoBallarotto MarcoAinsley JonMeister PaulSethi DebaratiBurke RosemaryScarpino AndreaLe Bihan Yann-VaïGrädler UlrichBlagg JulianWorkman PaulClarke Paul ABlum AndreasEsdar ChristinaBhalay Gurdipvan Montfort Rob L M - DHX8 encodes a DEAH-box RNA helicase, an ATP-dependent enzyme that plays essential roles in RNA metabolism, including pre-mRNA splicing, transcription, and mRNA decay. Although DHX8 dysfunction has been linked with developmental abnormalities and disease pathogenesis in multiple model organisms, its biological functions in Lepidoptera, particularly in the silkworm , remain unknown. To investigate the developmental role of . DHX8 (BmDHX8), we generated knockout mutants using CRISPR-Cas9 genome editing. Genome sequencing confirmed frameshift mutations in the BmDHX8 locus. BmDHX8 mutants exhibited severe developmental defects such as dramatically reduced body size and premature lethality of silkworm larvae. Molecular characterization suggested systemic dysregulation, as evidenced by decreased triglyceride accumulation, impaired mTOR signaling activity, and increased aberrant splicing events. Therefore, these results indicate that loss of BmDHX8 is associated with aberrant splicing and alterations in lipid homeostasis and mTOR signaling pathways, potentially contributing to developmental defects. Taken together, our study offers an initial functional knockout analysis of BmDHX8 in regulating larval development in silkworms. - Source: PubMed
Publication date: 2026/02/25
Ding LingXu CexinZhang YunxiaoWang YuanboHou YongShen GuanwangLin PingXia QingyouZhao PingLi Zhiqing - Transcription factor heat shock factor 1 (HSF1) orchestrates the cellular stress response, promoting malignant transformation, unchecked proliferation, and stress-resilient survival of tumour cells. We set out to discover potentially druggable regulators of HSF1 activation and identified DEAH-box RNA helicase 8 (DHX8). We investigated the role of DHX8 in regulating HSF1 within the broader context of DHX8 function in cancer cells. DHX8 silencing induces intron retention in transcripts, reducing HSF1 protein. Importantly, DHX8 loss significantly alters RNA processing of an HSF1-regulated cancer-associated gene signature linked to poor clinical outcomes, as well as additional oncogenic and stress-response pathways. DHX8 binds between the pre-messenger RNA (mRNA) lariat branch point and the 3' splice site, consistent with the predominance of intron-retained transcripts following DHX8 loss. We show that both the ATPase and RNA-binding activities of DHX8 are essential for its role in splicing, including processing of mRNA. We also find that DHX8 silencing triggers apoptosis more effectively in human cancer cells than in non-tumorigenic cells. Our findings identify DHX8 as a critical regulator of stress-adaptive gene expression, highlighting its promise as a therapeutic target not only to disrupt HSF1-dependent transcriptional programs but also having broader effects in cancer cells under oncogenic stress. - Source: PubMed
Publication date: 2026/03/12
Tall Jennifer RTe Poele RobertVasile AlexandraRamagiri PradeepCampbell JamesDavies Caitlin RPowers Marissa VRoe TobySankaran DeivendranWang HannahMitsopoulos KonstantinosAl-Lazikani Bissanvan Montfort Rob L Mde Billy EmmanuelWorkman PaulClarke Paul A - Pre-mRNA splicing is orchestrated by the spliceosome through coordinated RNA and protein rearrangements driven by ATP-dependent RNA helicases. DEAH-box helicases serve as principal motors, controlling catalytic activation, exon ligation, and complex disassembly. Early mechanistic understanding was limited by low-resolution cryo-electron microscopy (cryo-EM) structures, leaving RNA substrate interactions largely inferred from biochemical and genetic studies. Recent high-resolution cryo-EM structures (2021-present) have captured all five spliceosomal DEAH-box helicases-DHX16/Prp2, DHX38/Prp16, DHX8/Prp22, DHX15/Prp43, and DHX35-bound to their RNA targets within distinct spliceosomal states. These structures reveal precise recruitment, substrate recognition, and stage-specific actions. In this review, I integrate these insights into a unified framework, highlighting structural, biochemical, and evolutionary perspectives to guide future investigations of helicase regulation and their role in maintaining the fidelity of eukaryotic RNA splicing. - Source: PubMed
Chen Zhe - : Using fish collagen supplements in daily nutrition may positively influence health and healthy aging. However, their systemic, molecular-level effects on humans are not well characterized. Therefore, given the scarcity of proteomic data, this study aimed to assess the serum proteomic changes during the fish collagen supplementation in healthy women. : This was a crossover interventional study. Thirty healthy women received either 5 mL of fish gel collagen (from silver carp: ) supplementation with 200 mL of pure water for 40 days or 200 mL of pure water for 40 days only. The washout between the fish collagen and pure water supplementation was 40 days. The nutritional status and dietary intake were assessed. Proteome analyses were conducted using a MALDI-TOF mass spectrometer in a positive linear mode in the / 1000-10,000 range. : The diet of the women in this study was not well-balanced. Supplementation did not affect nutritional status. Only water content significantly increased. During the fish collagen supplementation, the following discriminative proteins were identified: Filamin-A, Filamin-B, actin, Vimentin, Tropomyosin beta chain, 40S ribosomal protein S8, ATP-dependent RNA helicase DHX8, and FERM domain-containing protein 4A. : Changes in serum proteins may reflect broader cytoskeletal remodeling and cellular adaptation resulting from collagen intake. - Source: PubMed
Publication date: 2025/09/24
Stelmach-Mardas MartaMatuszewska-Mach ElizaKustra KrzysztofPietkiewicz DagmaraMatysiak JanHojan-Jezierska DorotaMardas MarcinKubisz Leszek