Affinage

DDX24

ATP-dependent RNA helicase DDX24 · UniProt Q9GZR7

Length
859 aa
Mass
96.3 kDa
Annotated
2026-06-09
27 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX24 is a ubiquitously expressed nucleolar DEAD-box RNA helicase that integrates ribosome biogenesis with post-transcriptional control of specific mRNAs governing cell proliferation, vascular biology, and innate immunity (PMID:10936056, PMID:24980433, PMID:37705750). In the nucleolus it associates with NPM1 to regulate liquid-liquid phase separation of the granular component and supports ribosome biogenesis, with disease-associated mutations disrupting nucleolar partitioning and morphology (PMID:37705750); its incorporation into pre-rRNP processing complexes for early pre-rRNA processing requires MDM2-mediated non-proteolytic polyubiquitylation, and DDX24 loss impairs pre-rRNA processing and stabilizes p53 (PMID:24980433). DDX24 also restrains the p53 pathway directly by binding p300 and suppressing p300-mediated p53 acetylation (PMID:25867071). As a sequence-specific RNA-binding protein, DDX24 directly binds and stabilizes target transcripts including LAMB1, FANCA, and PPFIA4 (PMID:35763670, PMID:37470182, PMID:41105514), promotes decay of CLEC14A and ERG mRNAs through the CCR4-NOT deadenylase complex (PMID:41728947), and acts as a splicing factor on IKBKG pre-mRNA (PMID:39897555); through these targets and direct binding of VEGFR2 mRNA it controls endothelial migration, tube formation, angiogenesis, and blood-brain-barrier integrity, and point mutations in DDX24 (including the ATP-binding domain) are associated with vascular malformations (PMID:30063812, PMID:37470182, PMID:40339127, PMID:41105514). In innate immunity DDX24 negatively regulates RIG-I-like receptor signaling by associating with FADD and RIP1 to impede IRF7 (PMID:24204270). DDX24 abundance is itself controlled post-translationally by TRIM27-mediated ubiquitination, which is blocked by LINC02551, and by SNRPF-dependent splicing that prevents NMD of its transcript (PMID:36335087, PMID:42107058).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 Medium

    Established DDX24 as a bona fide DEAD-box helicase family member, defining the molecular class and chromosomal locus before any function was known.

    Evidence cDNA cloning, Northern blot, and radiation hybrid mapping of the human gene

    PMID:10936056

    Open questions at the time
    • No enzymatic helicase activity demonstrated
    • No cellular function or RNA targets identified
    • Localization not yet resolved
  2. 2008 Medium

    First functional link to RNA metabolism, showing DDX24 acts in Rev/RRE-dependent viral RNA export via direct interaction with HIV-1 Rev.

    Evidence siRNA knockdown, viral packaging/infectivity assays, and Co-IP in human cells

    PMID:18289627

    Open questions at the time
    • Endogenous host RNA targets not addressed
    • Mechanism of export specificity unresolved
  3. 2013 High

    Defined DDX24 as a negative regulator of RLR innate immune signaling, connecting it to FADD/RIP1 adaptors and IRF7 suppression and demonstrating an essential developmental role.

    Evidence Reciprocal Co-IP, IRF7 reporter assays, RNA/DNA binding, and embryonic lethality on loss

    PMID:24204270

    Open questions at the time
    • Helicase catalytic requirement for immune suppression not tested
    • Direct RNA substrates in this pathway unknown
  4. 2014 High

    Placed DDX24 in nucleolar pre-rRNA processing and the MDM2-p53 axis, showing MDM2 non-proteolytically polyubiquitylates DDX24 to enable its recruitment to pre-rRNP complexes.

    Evidence In vitro/in vivo ubiquitylation, Co-IP, pre-rRNA processing and p53 stabilization assays

    PMID:24980433

    Open questions at the time
    • Ubiquitin chain linkage type not fully defined
    • Which pre-rRNA processing step DDX24 catalyzes unresolved
  5. 2015 High

    Identified a second, ribosome-independent route by which DDX24 restrains p53: direct p300 binding to block p53 acetylation and dampen p53 target transcription.

    Evidence Reciprocal Co-IP, acetylation assays, knockdown with cell cycle/senescence readouts

    PMID:25867071

    Open questions at the time
    • Whether RNA binding is required for p300 inhibition unknown
    • Structural basis of DDX24-p300 contact undefined
  6. 2019 Medium

    Linked DDX24 point mutations, including ATP-binding-domain residues, to human vascular malformations and to suppression of endothelial migration/tube formation.

    Evidence Genetic sequencing, structural modeling, endothelial knockdown functional assays

    PMID:30063812

    Open questions at the time
    • Molecular mechanism connecting mutation to endothelial phenotype not resolved
    • Causal RNA targets not identified
  7. 2022 Medium

    Established DDX24 as a sequence-specific mRNA-stabilizing factor and a regulator of ribosomal protein turnover, with targets driving cancer phenotypes.

    Evidence RNA-IP with defined binding sites, mRNA stability assays, Co-IP with nucleolin and RPL5, ubiquitination/stability assays, xenografts

    PMID:35763670 PMID:35864588

    Open questions at the time
    • How DDX24 selects target transcripts not defined
    • Helicase activity contribution to stabilization untested
  8. 2022 Medium

    Showed DDX24 protein level is controlled by TRIM27-mediated ubiquitination, antagonized by LINC02551 acting as a decoy adaptor.

    Evidence Co-IP, ubiquitination assays, RNA pulldown, lincRNA gain/loss

    PMID:36335087

    Open questions at the time
    • TRIM27 ubiquitination site on DDX24 not mapped
    • Physiological contexts triggering this control unknown
  9. 2022 Medium

    Demonstrated DDX24 binds viral immediate-early/early mRNAs and suppresses KSHV lytic reactivation, and that conserved residues support proliferation, broadening its antiviral and growth roles.

    Evidence RIP-seq, lytic reactivation assays; mutant cell lines with proliferation/nucleoli readouts; planarian RNAi epistasis

    PMID:35370459 PMID:35523320 PMID:36298642

    Open questions at the time
    • Mechanism linking viral mRNA binding to transcription suppression unclear
    • Conserved-residue mutants' biochemical defects undefined
  10. 2023 High

    Resolved a nucleolar phase-separation function via NPM1 and a vascular mRNA-stabilization program via FANCA, connecting ribosome biogenesis defects to endothelial/VSMC pathology.

    Evidence In vitro LLPS, Co-IP with NPM1, patient-tissue IF; conditional Ddx24 knockout mice, RNA-IP/pulldown, FANCA rescue

    PMID:37470182 PMID:37705750

    Open questions at the time
    • How mutations alter NPM1 client behavior mechanistically unresolved
    • Relationship between rRNA and mRNA functions not unified
  11. 2025 High

    Expanded the direct mRNA-target repertoire and tissue contexts, defining VEGFR2-binding-driven angiogenesis, PPFIA4-stabilization-driven BBB integrity, and IKBKG pre-mRNA splicing control of autophagy.

    Evidence Zebrafish and endothelial-specific knockout models, RNA-IP/binding assays, spatial transcriptomics, splicing analysis, pharmacological epistasis

    PMID:39897555 PMID:40339127 PMID:41105514

    Open questions at the time
    • Determinants of target-specific stabilization vs splicing outcomes unknown
    • Whether helicase catalysis is required across these targets untested
  12. 2026 High

    Defined a decay arm of DDX24 function, linking direct binding of CLEC14A/ERG mRNAs to the CCR4-NOT deadenylase complex, and showed DDX24 abundance is gated by SNRPF-dependent splicing/NMD.

    Evidence irCLIP-seq, mRNA stability assays, Co-IP with CCR4-NOT; transcriptomic intron-retention and NMD analyses with ASOs

    PMID:41728947 PMID:42107058

    Open questions at the time
    • What switches DDX24 between stabilizing and destabilizing modes is unknown
    • Recruitment mechanism to CCR4-NOT on specific transcripts undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single helicase reconciles opposing post-transcriptional outcomes (mRNA stabilization, decay via CCR4-NOT, and splicing) on different targets, and whether its catalytic ATPase/helicase activity drives these, remains unresolved.
  • No direct demonstration of ATP-dependent helicase activity on target RNAs
  • No unifying rule for target selection or outcome
  • No structural model of DDX24-RNA or DDX24-complex assemblies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0098772 molecular function regulator activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005730 nucleolus 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-168256 Immune System 1
Complex memberships
CCR4-NOT deadenylase complexpre-ribosomal ribonucleoprotein (pre-rRNP) processing complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 DDX24 was cloned and characterized as a DEAD-box protein containing all conserved DEAD-box motifs; it is ubiquitously expressed across human tissues and localized to human chromosome 14q32. cDNA cloning, Northern blot analysis, radiation hybrid mapping, genomic sequence analysis Genomics Medium 10936056
2008 DDX24 knockdown inhibits HIV-1 RNA packaging and viral infectivity specifically in the context of Rev/RRE-dependent (but not CTE-dependent) nuclear export of viral RNA, and DDX24 physically interacts with the HIV-1 Rev protein. siRNA knockdown, viral infectivity assays, RNA packaging assays, co-immunoprecipitation (DDX24–Rev interaction) Virology Medium 18289627
2013 DDX24 negatively regulates RIG-I-like receptor (RLR)-mediated innate immune signaling by associating with adaptor proteins FADD and RIP1, preferentially impeding IRF7 activity; DDX24 preferentially binds RNA over DNA, and its loss augments cytosolic RNA-mediated innate signaling. Overexpression and siRNA knockdown assays, co-immunoprecipitation (DDX24–FADD, DDX24–RIP1), IRF7 reporter assays, RNA/DNA binding assays, embryonic lethality phenotype upon DDX24 loss PLoS pathogens High 24204270
2014 MDM2 interacts with DDX24 via its central region and mediates non-proteolytic polyubiquitylation of DDX24 both in vitro and in vivo; this polyubiquitylation promotes DDX24 association with pre-ribosomal ribonucleoprotein (pre-rRNP) processing complexes required for early pre-rRNA processing. Depletion of DDX24 impairs pre-rRNA processing, abrogates MDM2 function, and leads to p53 stabilization. Co-immunoprecipitation, in vitro and in vivo ubiquitylation assays, siRNA knockdown, pre-rRNA processing assays, p53 stabilization assay Molecular and cellular biology High 24980433
2015 DDX24 interacts with p300 and suppresses p300-mediated acetylation of p53, thereby inhibiting p53 transcriptional targets (p21, PUMA). DDX24 knockdown increases p53 acetylation and promotes p53-dependent cell cycle arrest and senescence. Co-immunoprecipitation (DDX24–p300), acetylation assays, siRNA knockdown, p53 target gene expression analysis, cell cycle and senescence assays Oncogene High 25867071
2019 Point mutations in DDX24 (including ones in the ATP-binding domain) are associated with vascular malformations; DDX24 knockdown in endothelial cells results in elevated migration and tube formation, indicating a role for DDX24 in suppressing endothelial cell function. Genetic sequencing, structural modeling, siRNA knockdown, endothelial cell migration and tube formation assays, transcriptomic analysis Hepatology Medium 30063812
2022 DDX24 binds the mRNA of LAMB1 (at nucleotides 618–624) and stabilizes it in a manner dependent on interaction between nucleolin and the C-terminal region of DDX24, thereby promoting HCC migration and proliferation. RNA immunoprecipitation, mRNA stability assays, co-immunoprecipitation (DDX24–nucleolin), overexpression and knockdown, in vivo xenograft Cancer research Medium 35763670
2022 DDX24 interacts with RPL5 and promotes its ubiquitination and degradation, thereby promoting NSCLC metastasis. Co-immunoprecipitation followed by mass spectrometry, ubiquitination assays, protein stability assays, Transwell/wound-healing assays, in vivo xenograft Cancer medicine Medium 35864588
2022 DDX24 and DDX49 bind predominantly immediate-early and early KSHV mRNAs (identified by RNA immunoprecipitation followed by next-generation sequencing) and their overexpression suppresses KSHV lytic reactivation, reducing viral gene transcription and genome replication. RNA immunoprecipitation sequencing (RIP-seq), overexpression studies, KSHV lytic reactivation assays, interferon induction assays Viruses Medium 36298642
2022 DDX24 is enriched in planarian muscles; its knockdown disrupts muscle fiber organization, leading to defective pole specification and misregulation of positional control genes during regeneration, and upregulates wound-induced Wnt signaling. Suppressing ectopic Wnt activity rescues the knockdown phenotype. RNAi knockdown, immunofluorescence, genetic epistasis (Wnt inhibition rescuing DDX24-KD phenotype), in situ hybridization Developmental biology Medium 35523320
2022 LINC02551 acts as a molecular adaptor that blocks the interaction between DDX24 and the E3 ligase TRIM27, thereby preventing ubiquitination and degradation of DDX24. Co-immunoprecipitation, ubiquitination assays, RNA pulldown, lincRNA knockdown/overexpression Cell death & disease Medium 36335087
2022 DDX24 mutations K11E and E271K represent loss-of-function for cell proliferation; cells expressing these mutants show decreased nucleoli number, slower proliferation, and lower colony formation rates compared to wild-type DDX24. Stable cell line construction, immunofluorescence (nucleoli counting), proliferation and colony formation assays, in vivo tumor-bearing mouse model with 18F-FDG PET/CT, transcriptome sequencing International journal of medical sciences Medium 35370459
2023 DDX24 is mainly located in the nucleolus; disease-associated mutant DDX24-E271K partitions less into nucleoli in patient tissues and endothelial cells, altering nucleolar morphology. DDX24 physically associates with NPM1 and regulates its liquid-liquid phase separation behavior as a client in the nucleolar granular component. DDX24 mutation or knockdown disrupts ribosome biogenesis and elevates endothelial cell migration and tube formation. In vitro condensate assay (LLPS), co-immunoprecipitation (DDX24–NPM1), immunofluorescence in patient tissues and cultured endothelial cells, siRNA knockdown, ribosome biogenesis assay, migration and tube formation assays International journal of biological sciences High 37705750
2023 DDX24 binds FANCA mRNA and stabilizes it, promoting VSMC proliferation and cell cycle progression. VSMC-specific Ddx24 knockout mice die before embryonic day 13.5 with vascular defects; FANCA overexpression rescues cell cycle and DNA repair defects caused by DDX24 deficiency. Conditional knockout mice (Tagln-Cre), RNA immunoprecipitation with qRT-PCR, RNA pulldown, mRNA stability assays, RNA sequencing, flow cytometry, cell proliferation assays, rescue experiments Arteriosclerosis, thrombosis, and vascular biology High 37470182
2023 DDX24 binds HK1 mRNA and positively regulates HK1 expression, promoting glycolysis (glucose uptake and lactate production) in gastric cancer cells. RNA immunoprecipitation, glucose uptake and lactate production assays, DDX24 overexpression/knockdown, cell proliferation and migration assays Cellular signalling Low 38043669
2024 Endothelium-targeted Ddx24 conditional knockout mice show no developmental abnormality but exhibit vascular hyperpermeability upon ConA challenge, exacerbating immune-mediated hepatitis via upregulation of TNF-α and IFN-γ and downregulation of vascular integrity-associated proteins. CRISPR/Cas9-mediated Cre-loxP conditional knockout mice, mass spectrometry of liver proteins, endothelial migration and tube formation assays, in vivo ConA hepatitis model, cytokine measurement International immunopharmacology Medium 38354508
2025 DDX24 deficiency in zebrafish enhances VEGFR2 expression by directly binding to its mRNA in non-brain endothelial cells, while suppressing GPR124/RECK-mediated Wnt signaling in brain endothelial cells, causing spatially distinct angiogenesis phenotypes (intersegmental vessel hyperbranching vs. inhibited central artery angiogenesis). Zebrafish DDX24 knockout, RNA binding assays (mRNA binding), spatial transcriptomics, pharmacological rescue experiments, in vivo imaging PNAS High 40339127
2025 DDX24 binds PPFIA4 mRNA and enhances its stability in cerebral microvascular endothelial cells; PPFIA4 knockdown impairs mitochondrial homeostasis and barrier function. Endothelial-specific Ddx24 knockout mice show increased BBB permeability and learning/memory deficits. DDX24 knockdown causes occludin phosphorylation and mitochondrial dysfunction, reversed by NADPH oxidase inhibition. Endothelial-specific Ddx24 conditional knockout mice, RNA immunoprecipitation (DDX24–PPFIA4 mRNA), mRNA stability assay, occludin phosphorylation assay, BBB permeability assay, behavioral tests, pharmacological NADPH oxidase inhibition Cell reports High 41105514
2025 DDX24 functions as a splicing factor that directly binds IKBKG pre-mRNA; DDX24 ablation stimulates generation of the long splicing isoform of IKBKG, which promotes autophagy through NF-κB signaling and BECN1 transcription, thereby suppressing lung cancer growth. Mass spectrometry, RNA sequencing (alternative splicing analysis), co-immunoprecipitation, luciferase reporter assays, functional rescue experiments, xenograft tumor models Theranostics Medium 39897555
2025 DDX24 regulates transcription of heme oxygenase-1 (HO-1) at the promoter/enhancer E1 region level (not by mRNA stability), thereby exerting anti-apoptotic and anti-oxidative effects under oxidative stress conditions. RNA sequencing, DDX24 knockdown and overexpression, HO-1 expression and mRNA stability assays, promoter/enhancer reporter assay, cell viability assays FASEB journal Low 40847746
2026 DDX24 promotes mRNA decay of CLEC14A and ERG mRNAs in endothelial cells by directly binding these transcripts and promoting their degradation in a CCR4-NOT deadenylase complex-dependent manner, thereby modulating endothelial cell functions critical for angiogenesis. Infrared cross-linking immunoprecipitation sequencing (irCLIP-seq), mRNA stability assays, co-immunoprecipitation (DDX24–CCR4-NOT complex), endothelial cell functional assays Nucleic acids research High 41728947
2026 SNRPF-mediated splicing controls DDX24 protein abundance: SNRPF depletion induces intron 6 retention in DDX24 pre-mRNA, disrupting the Helicase_C domain and generating premature termination codons that trigger nonsense-mediated decay (NMD), reducing DDX24 protein levels. Integrated transcriptomic and proteomic analyses, intron retention analysis, antisense oligonucleotide experiments, NMD pathway validation, xenograft models Advanced science Medium 42107058

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling. PLoS pathogens 76 24204270
2008 The requirement of the DEAD-box protein DDX24 for the packaging of human immunodeficiency virus type 1 RNA. Virology 51 18289627
2022 ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis. Cell death & disease 43 36335087
2015 Negative regulation of the p300-p53 interplay by DDX24. Oncogene 43 25867071
2022 RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression. Cancer research 30 35763670
2014 MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Molecular and cellular biology 19 24980433
2019 DDX24 Mutations Associated With Malformations of Major Vessels to the Viscera. Hepatology (Baltimore, Md.) 17 30063812
2022 DDX24 promotes metastasis by regulating RPL5 in non-small cell lung cancer. Cancer medicine 15 35864588
2000 Cloning and characterization of human DDX24 and mouse Ddx24, two novel putative DEAD-Box proteins, and mapping DDX24 to human chromosome 14q32. Genomics 14 10936056
2023 DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA. Arteriosclerosis, thrombosis, and vascular biology 10 37470182
2023 DDX24 Mutation Alters NPM1 Phase Behavior and Disrupts Nucleolar Homeostasis in Vascular Malformations. International journal of biological sciences 10 37705750
2025 Loss of DDX24 inhibits lung cancer progression by stimulating IKBKG splicing-mediated autophagy. Theranostics 8 39897555
2023 DDX24 promotes tumor progression by mediating hexokinase-1 induced glycolysis in gastric cancer. Cellular signalling 8 38043669
2022 DExD/H Box Helicases DDX24 and DDX49 Inhibit Reactivation of Kaposi's Sarcoma Associated Herpesvirus by Interacting with Viral mRNAs. Viruses 7 36298642
2022 DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration. Developmental biology 6 35523320
2025 DDX24 spatiotemporally orchestrates VEGF and Wnt signaling during developmental angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 5 40339127
2022 DDX24 regulates the chemosensitivity of hepatocellular carcinoma to sorafenib via mediating the expression of SNORA18. Cancer biology & therapy 4 36310384
2022 Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity. International journal of medical sciences 3 35370459
2024 Endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice due to vascular hyper-permeability. International immunopharmacology 1 38354508
2026 DDX24 modulates angiogenesis by promoting CCR4-NOT complex-dependent mRNA decay. Nucleic acids research 0 41728947
2026 Immunomodulatory Roles and Clinical Significance of GZMM and DDX24 in Sepsis: A Multiomics Integrative Analysis With Experimental Validation. Human mutation 0 41948606
2026 CSTA and DDX24: potential biomarkers regulating ferroptosis in sepsis and their diagnostic value. BMC medical genomics 0 41952180
2026 Disruption of the SNRPF-DDX24-E2F4 Feedback Loop Uncouples Splicing and Transcriptional Regulation to Suppress Ovarian Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42107058
2026 DDX24 exacerbates inflammation-induced immunosuppression in oral squamous cell carcinoma progression through IL-17 signaling pathway. Archives of oral biology 0 42208160
2025 DDX24 inhibits clear cell renal cell carcinoma progression by directly regulating AKR1B10. Cellular signalling 0 40216172
2025 Anti-Apoptotic and Anti-Oxidative Effects of DDX24 Through HO-1 Transcriptional Regulation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40847746
2025 DEAD-box helicase DDX24 is essential for endothelial mitochondrial function to maintain the blood-brain barrier. Cell reports 0 41105514

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