Affinage

DDX24

ATP-dependent RNA helicase DDX24 · UniProt Q9GZR7

Length
859 aa
Mass
96.3 kDa
Annotated
2026-04-28
24 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX24 is a DEAD-box RNA helicase that functions as a multifaceted post-transcriptional and transcriptional regulator essential for ribosome biogenesis, vascular development, and innate immune homeostasis. DDX24 directly binds specific mRNAs—including LAMB1, FANCA, VEGFR2, PPFIA4, and IKBKG—to regulate their stability or alternative splicing, and promotes CCR4-NOT-dependent mRNA decay of endothelial transcripts such as CLEC14A and ERG to control angiogenesis (PMID:41728947, PMID:37470182, PMID:40339127, PMID:39897555). In the nucleolus, MDM2-mediated nonproteolytic polyubiquitylation of DDX24 facilitates its association with pre-rRNP complexes required for pre-rRNA processing, and DDX24 regulates nucleolar organization through NPM1-dependent liquid–liquid phase separation (PMID:24980433, PMID:37705750). DDX24 additionally suppresses p53 activation by inhibiting p300-mediated p53 acetylation, attenuates RLR-mediated type I interferon responses by associating with FADD and RIP1, and is itself subject to TRIM27-mediated proteasomal degradation counteracted by the lncRNA LINC02551 (PMID:25867071, PMID:24204270, PMID:36335087).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Medium

    Identification of DDX24 as a conserved DEAD-box family member established it as a candidate RNA helicase, but its cellular function remained unknown.

    Evidence cDNA cloning, Northern blot, and radiation hybrid mapping in human tissues

    PMID:10936056

    Open questions at the time
    • No enzymatic or functional assay performed
    • Helicase activity not demonstrated
    • No subcellular localization determined
  2. 2008 Medium

    Linking DDX24 to HIV-1 Rev-dependent RNA packaging provided the first functional evidence that DDX24 participates in nuclear RNA export and viral RNA metabolism.

    Evidence siRNA knockdown, HIV-1 RNA packaging assay, and Co-IP of DDX24–Rev interaction

    PMID:18289627

    Open questions at the time
    • Whether DDX24 directly unwinds viral RNA structures not tested
    • Role in endogenous mRNA export not addressed
    • Single viral system
  3. 2013 High

    Discovery that DDX24 suppresses RLR-mediated type I interferon signaling through FADD/RIP1 interaction established it as a negative regulator of innate immunity, revealing a non-canonical function beyond RNA metabolism.

    Evidence Overexpression/knockdown reporter assays, Co-IP of DDX24–FADD and DDX24–RIP1, RNA vs. DNA binding assays

    PMID:24204270

    Open questions at the time
    • Precise mechanism of IRF7 inhibition not defined at the structural level
    • Whether helicase activity is required for immune suppression not tested
  4. 2014 High

    Demonstrating that MDM2 mediates nonproteolytic polyubiquitylation of DDX24 to promote its association with pre-rRNP complexes resolved how DDX24 enters the ribosome biogenesis pathway and connected ribosomal stress to p53 stabilization.

    Evidence In vitro and in vivo ubiquitylation assays, Co-IP of DDX24–MDM2, pre-rRNA processing assays, p53 stabilization readout

    PMID:24980433

    Open questions at the time
    • Which specific pre-rRNA processing step DDX24 catalyzes remains unclear
    • Ubiquitylation sites on DDX24 not mapped
    • Direct helicase activity on pre-rRNA not shown
  5. 2015 High

    Finding that DDX24 inhibits p300-mediated p53 acetylation explained how DDX24 depletion activates p53 target genes (p21, PUMA), linking DDX24 to cell cycle control and senescence independently of ribosomal stress.

    Evidence Co-IP of DDX24–p300 and p300–p53, acetylation assays, siRNA knockdown with cell cycle and senescence readouts

    PMID:25867071

    Open questions at the time
    • Whether the DDX24–p300 interaction requires RNA binding or helicase activity is unknown
    • Relationship between nucleolar and p300-mediated p53 regulation not dissected
  6. 2019 Medium

    Identification of DDX24 mutations (K11E, E271K) in patients with vascular malformations provided the first genetic evidence that DDX24 loss-of-function causes human vascular disease, linking its molecular functions to endothelial biology.

    Evidence Genetic mutation analysis, siRNA knockdown in endothelial cells with migration and tube formation assays

    PMID:30063812

    Open questions at the time
    • Causal mechanism by which mutations cause vascular malformations not fully defined
    • Patient cohort limited
  7. 2022 Medium

    Multiple studies in 2022 established DDX24 as a direct mRNA-binding protein that stabilizes LAMB1 mRNA (via nucleolin interaction), promotes RPL5 ubiquitination and degradation, and suppresses KSHV lytic replication, broadening its role to post-transcriptional regulation and cancer cell proliferation.

    Evidence RNA immunoprecipitation, mRNA stability assays, Co-IP/MS (DDX24–RPL5, DDX24–nucleolin), RIP-seq in KSHV-infected cells, knockdown/overexpression with functional readouts

    PMID:35763670 PMID:35864588 PMID:36298642

    Open questions at the time
    • Whether mRNA stabilization requires helicase activity is untested
    • RPL5 ubiquitination mechanism (direct vs. adaptor) unclear
    • KSHV antiviral mechanism is descriptive
  8. 2022 Medium

    Demonstration that TRIM27 ubiquitylates DDX24 for proteasomal degradation and that LINC02551 blocks this interaction revealed a regulatory axis controlling DDX24 protein levels in hepatocellular carcinoma, connecting m6A RNA modification to DDX24 abundance.

    Evidence Co-IP of DDX24–TRIM27, ubiquitination assays, m6A modification analysis, functional rescue

    PMID:36335087

    Open questions at the time
    • TRIM27 ubiquitination sites on DDX24 not mapped
    • Single cancer type studied
    • LINC02551 structural basis for blocking TRIM27 unknown
  9. 2023 Medium

    Showing that DDX24 associates with NPM1 and modulates nucleolar liquid–liquid phase separation explained how DDX24 mutations disrupt nucleolar organization and ribosome biogenesis, connecting phase behavior to the vascular phenotype.

    Evidence In vitro biomolecular condensate assay, Co-IP of DDX24–NPM1, immunofluorescence in patient tissues, knockdown/mutation functional assays

    PMID:37705750

    Open questions at the time
    • Whether DDX24 helicase activity drives phase separation partitioning not tested
    • Contribution of phase separation vs. enzymatic activity to ribosome biogenesis not separated
  10. 2023 High

    Conditional VSMC-specific Ddx24 knockout causing embryonic lethality before E13.5 with defective vessel formation, rescued by FANCA overexpression, established DDX24-dependent FANCA mRNA stabilization as essential for vascular smooth muscle cell survival and vessel integrity.

    Evidence VSMC-specific Cre-loxP knockout mice, RNA immunoprecipitation, mRNA stability assay, FANCA rescue

    PMID:37470182

    Open questions at the time
    • DDX24 binding site on FANCA mRNA not mapped at nucleotide resolution
    • Whether other mRNA targets contribute to the VSMC lethal phenotype not excluded
  11. 2025 High

    Several 2025 studies revealed DDX24 as a versatile mRNA regulator in the vasculature: it directly binds VEGFR2 mRNA to limit angiogenic sprouting in zebrafish, stabilizes PPFIA4 mRNA to maintain blood-brain barrier integrity, and regulates IKBKG pre-mRNA splicing to control NF-κB-driven autophagy in lung cancer.

    Evidence Zebrafish morpholino/mutant with pharmacological epistasis, endothelial-specific Ddx24 KO mice with BBB permeability and behavioral tests, RNA-seq-based alternative splicing analysis with functional rescue in xenografts

    PMID:39897555 PMID:40339127 PMID:41105514

    Open questions at the time
    • Structural basis for DDX24 target mRNA selectivity not resolved
    • Whether splicing regulation is direct unwinding or scaffolding is unclear
    • Brain vs. non-brain endothelial target specificity mechanism unknown
  12. 2025 Medium

    Identification of DDX24 as a transcriptional regulator of HO-1 under oxidative stress, acting at the promoter/enhancer rather than on mRNA stability, expanded its functional repertoire beyond post-transcriptional regulation.

    Evidence HO-1 promoter/enhancer reporter assays, mRNA stability assay ruling out post-transcriptional effect, knockdown/overexpression with oxidative stress readouts

    PMID:40847746

    Open questions at the time
    • Whether DDX24 binds chromatin directly or acts through a transcription factor complex unknown
    • Mechanism distinguishing transcriptional from post-transcriptional target selection unclear
  13. 2026 High

    Transcriptome-wide iCLIP-seq mapping of DDX24 binding sites coupled with demonstration of CCR4-NOT complex interaction established that DDX24 recruits the deadenylase machinery to specific endothelial mRNAs to promote their decay, providing a unifying mechanism for its mRNA-destabilizing activities.

    Evidence iCLIP-seq for direct binding, Co-IP of DDX24–CCR4-NOT complex, mRNA decay assays in endothelial cells

    PMID:41728947

    Open questions at the time
    • Whether DDX24 helicase activity is required for CCR4-NOT recruitment not tested
    • How DDX24 distinguishes mRNAs it stabilizes from those it promotes for decay is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A central unresolved question is how DDX24 selects between stabilizing and destabilizing mRNA targets, and whether its enzymatic helicase activity—as opposed to scaffolding—is required for each of its diverse functions in ribosome biogenesis, mRNA regulation, innate immunity, and transcription.
  • No crystal or cryo-EM structure of DDX24 alone or in complex
  • Helicase activity has never been directly measured in vitro on any substrate
  • Selectivity rules for mRNA stabilization vs. CCR4-NOT-dependent decay are unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0140098 catalytic activity, acting on RNA 5 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 3
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-74160 Gene expression (Transcription) 1 R-HSA-9612973 Autophagy 1
Partners
EP300FADDMDM2NCLNPM1RIP1TP53TRIM27
Complex memberships
CCR4-NOT deadenylase complex

Evidence

Reading pass · 20 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 with all conserved DEAD-box motifs, showing ubiquitous expression across human tissues and mapping to chromosome 14q32; the gene spans ~30 kb with at least nine exons. cDNA cloning, Northern blot, radiation hybrid mapping, genomic sequence comparison Genomics Medium 10936056
2008 DDX24 knockdown inhibits HIV-1 RNA packaging and viral infectivity specifically in the context of Rev/RRE-dependent nuclear export; DDX24 interacts with the HIV-1 Rev protein, indicating it acts at an early phase of viral RNA metabolism prior to nuclear export. siRNA knockdown, HIV-1 RNA packaging assay, co-immunoprecipitation (DDX24–Rev interaction), CTE vs. RRE comparison 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 to suppress type I IFN production; DDX24 preferentially binds RNA rather than DNA. DDX24 overexpression/knockdown in reporter assays, co-immunoprecipitation (DDX24–FADD and DDX24–RIP1), RNA vs. DNA binding assays, DDX24 loss-of-function (embryonic lethality model) PLoS pathogens High 24204270
2014 MDM2 interacts with the central region of DDX24 and mediates its nonproteolytic polyubiquitylation (both in vitro and in vivo); this ubiquitylation promotes DDX24 association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes required for early pre-rRNA processing steps; DDX24 depletion impairs pre-rRNA processing, abrogates MDM2 function, and leads to p53 stabilization. Co-immunoprecipitation (DDX24–MDM2), in vitro and in vivo ubiquitylation assays, pre-rRNA processing assays, DDX24 knockdown with p53 stabilization readout Molecular and cellular biology High 24980433
2015 DDX24 interacts with p300, suppressing p300-mediated acetylation of p53; DDX24 overexpression inhibits the p300–p53 interaction, while DDX24 knockdown increases endogenous p53 acetylation, activates p21 and PUMA expression, and induces cell cycle arrest and senescence in a p53-dependent manner. Co-immunoprecipitation (DDX24–p300, p300–p53), acetylation assays, siRNA knockdown, cell cycle and senescence assays Oncogene High 25867071
2019 DDX24 mutations (including K11E and E271K in the ATP-binding domain) are associated with vascular malformations; DDX24 knockdown in endothelial cells elevates migration and tube formation, establishing a functional role in endothelial cell behavior. Genetic mutation analysis, structural modeling, siRNA knockdown, endothelial cell migration and tube formation assays, transcriptomic analysis Hepatology Medium 30063812
2022 LINC02551 acts as a molecular adaptor that blocks the interaction between DDX24 and the E3 ubiquitin ligase TRIM27, thereby decreasing ubiquitination and proteasomal degradation of DDX24 and promoting HCC progression; ALKBH5-mediated m6A demethylation of LINC02551 destabilizes LINC02551 and consequently reduces DDX24 protein. Co-immunoprecipitation (DDX24–TRIM27), ubiquitination assay, m6A modification analysis, knockdown/overexpression functional assays Cell death & disease Medium 36335087
2022 DDX24 binds the LAMB1 mRNA (nt 618–624) and increases its stability in a manner dependent on interaction between nucleolin and the C-terminal region of DDX24, promoting HCC migration and proliferation. RNA immunoprecipitation, mRNA stability assay, Co-immunoprecipitation (DDX24–nucleolin), overexpression/knockdown with migration/proliferation readouts Cancer research Medium 35763670
2022 DDX24 and DDX49 bind predominantly to immediate-early and early KSHV mRNAs (shown by RNA immunoprecipitation followed by next-generation sequencing) and exert antiviral activity by suppressing lytic viral transcription and genome replication when overexpressed in BCBL-1 cells. RNA immunoprecipitation-seq (tagged DDX24), overexpression in BCBL-1 cells, viral gene expression and replication assays, RNA pulldown with candidate transcripts Viruses Medium 36298642
2022 DDX24 interacts with RPL5 and promotes its ubiquitination and destabilization in NSCLC cells, enhancing cancer cell migration and invasion. Co-immunoprecipitation followed by mass spectrometry, protein stability assay, ubiquitination assay, knockdown/overexpression migration and invasion assays Cancer medicine Medium 35864588
2022 Loss-of-function mutations K11E and E271K in DDX24 reduce nucleolar number and cell proliferation, consistent with DDX24's role as an oncogenic factor in the nucleolus; these mutations decrease tumor formation in mouse xenograft models and alter immune-related signaling pathways. Stable cell line expression of WT and mutant DDX24, immunofluorescence (nucleoli counting), proliferation/colony assays, xenograft mouse models, transcriptome sequencing International journal of medical sciences Medium 35370459
2023 DDX24 mutation E271K causes DDX24 to partition less into nucleoli; DDX24 directly associates with NPM1 and regulates its liquid-liquid phase separation behavior as a client in the nucleolar granular component; mutation or knockdown of DDX24 disrupts nucleolar homeostasis, impairs ribosome biogenesis, and elevates endothelial cell migration and tube formation. In vitro biomolecular condensate assay, Co-immunoprecipitation (DDX24–NPM1), immunofluorescence in patient tissues and ECs, knockdown and mutation functional assays (migration, tube formation, ribosome biogenesis) International journal of biological sciences Medium 37705750
2023 DDX24 binds FANCA mRNA and stabilizes it; DDX24 loss leads to decreased FANCA, increased DNA damage, and cell cycle arrest in vascular smooth muscle cells; overexpression of FANCA rescues the DDX24-deficiency phenotype; VSMC-specific Ddx24 knockout mice die before E13.5 with defective vessel formation. RNA immunoprecipitation with qRT-PCR, RNA stability assay (RNA pulldown), VSMC-specific Cre-loxP knockout mice, flow cytometry, cell proliferation assay, rescue with FANCA overexpression Arteriosclerosis, thrombosis, and vascular biology High 37470182
2023 DDX24 binds HK1 mRNA and positively regulates HK1 expression at the transcriptional level, promoting glycolysis (glucose uptake, lactate production) and tumor cell proliferation, migration, and invasion in gastric cancer. RNA binding assay (DDX24–HK1 mRNA), knockdown/overexpression with glycolysis readouts (glucose uptake, lactate), proliferation and migration assays Cellular signalling Low 38043669
2024 Endothelium-targeted Ddx24 conditional knockout (Cdh5-Cre system) in mice leads to elevated endothelial migration and tube formation, vascular hyper-permeability, and exacerbated ConA-induced hepatitis with elevated TNF-α and IFN-γ; mass spectrometry identified downregulation of vascular integrity-associated proteins. CRISPR/Cas9-mediated Cre-loxP conditional knockout, endothelial cell migration and tube formation assays, in vivo ConA hepatitis model, mass spectrometry of liver tissue proteins International immunopharmacology Medium 38354508
2025 DDX24 regulates alternative splicing of IKBKG pre-mRNA; DDX24 directly binds IKBKG pre-mRNA, and DDX24 ablation stimulates generation of the long IKBKG isoform, which activates NF-κB signaling, induces BECN1 transcription, and promotes autophagy to suppress lung cancer growth. Mass spectrometry (splicing interactome), RNA sequencing (alternative splicing), Co-immunoprecipitation, luciferase reporter assays, direct mRNA binding, xenograft tumor models, functional rescue with long IKBKG isoform Theranostics Medium 39897555
2025 DDX24 deficiency in zebrafish endothelium enhances VEGFR2 expression by direct binding to its mRNA in non-brain endothelial cells, causing intersegmental vessel hyperbranching; in brain endothelial cells, DDX24 deficiency suppresses GPR124/RECK-mediated Wnt signaling; pharmacological rescue of both pathways in temporal sequence corrects the vascular phenotypes. Zebrafish ddx24 morpholino/mutant, direct mRNA binding assay (VEGFR2 mRNA), spatial transcriptome analysis, pharmacological epistasis, endothelial cell-type-specific dissection PNAS High 40339127
2025 DDX24 binds PPFIA4 mRNA and enhances its stability; DDX24 knockdown reduces PPFIA4, causing occludin phosphorylation and mitochondrial dysfunction in cerebral microvascular endothelial cells; endothelial-specific Ddx24 KO mice show increased BBB permeability and learning/memory deficits; NADPH oxidase inhibition rescues these phenotypes. Endothelial-specific Ddx24 conditional knockout mice, RNA binding/stability assay (DDX24–PPFIA4 mRNA), Co-IP, occludin phosphorylation assay, mitochondrial function assay, NADPH oxidase inhibitor rescue, behavioral tests Cell reports High 41105514
2025 DDX24 regulates HO-1 gene transcription (not mRNA stability) under oxidative stress, likely acting at the HO-1 promoter and enhancer E1 region; DDX24 depletion reduces HO-1 expression, cell viability, and anti-apoptotic/anti-oxidative capacity. RNA sequencing (DDX24-depleted vs. overexpressing cells), HO-1 promoter/enhancer reporter assays, mRNA stability assay, knockdown/overexpression with apoptosis and oxidative stress readouts FASEB journal Medium 40847746
2026 DDX24 directly binds specific endothelial mRNAs (including CLEC14A and ERG) identified by iCLIP-seq, and promotes their decay through interaction with the CCR4-NOT deadenylase complex, thereby regulating angiogenesis. Infrared cross-linking immunoprecipitation sequencing (iCLIP-seq), Co-immunoprecipitation (DDX24–CCR4-NOT complex), mRNA decay assays, endothelial functional assays Nucleic acids research High 41728947

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling. PLoS pathogens 74 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 41 36335087
2015 Negative regulation of the p300-p53 interplay by DDX24. Oncogene 41 25867071
2022 RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression. Cancer research 28 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 9 37470182
2023 DDX24 Mutation Alters NPM1 Phase Behavior and Disrupts Nucleolar Homeostasis in Vascular Malformations. International journal of biological sciences 9 37705750
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 Loss of DDX24 inhibits lung cancer progression by stimulating IKBKG splicing-mediated autophagy. Theranostics 5 39897555
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
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