Affinage

DDX5

Probable ATP-dependent RNA helicase DDX5 · UniProt P17844

Length
614 aa
Mass
69.1 kDa
Annotated
2026-04-28
100 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDX5 (p68) is a DEAD-box RNA helicase that integrates nucleic acid remodeling with transcriptional regulation, RNA processing, and genome integrity maintenance. It possesses RNA-dependent ATPase, RNA helicase/annealing, G-quadruplex unfolding, and R-loop resolution activities, deploying these to regulate pre-mRNA splicing (by remodeling splice-site structures to modulate U1 snRNP access), circRNA biogenesis, miRNA processing via the Drosha/Microprocessor complex, and mRNA export (PMID:2471939, PMID:16107697, PMID:21343338, PMID:31548374, PMID:31267554, PMID:37019933, PMID:25963660, PMID:16598038). DDX5 serves as a context-dependent transcriptional coactivator or corepressor for numerous transcription factors—including p53, β-catenin, AR, ERα, RORγt, STAT3, Runx2, and c-Myc—by occupying target promoters, recruiting chromatin remodelers (NuRD complex, HDAC1), and resolving promoter G-quadruplex structures to facilitate transcription (PMID:15660129, PMID:17699760, PMID:26675721, PMID:31548374, PMID:24469041, PMID:36724232). Its diverse functions are modulated by post-translational modifications including SUMO-2 conjugation at K53 by PIAS1 (switching coactivation to repression), p300-mediated acetylation (stabilizing the protein and enhancing ERα coactivation), PRMT5-dependent arginine methylation of the RGG/RG motif (required for XRN2 recruitment and R-loop resolution), tyrosine phosphorylation at Y593, and O-GlcNAcylation by OGT (PMID:17369852, PMID:20663877, PMID:31267554, PMID:20676135, PMID:30484950).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1989 High

    Establishing that DDX5 is an RNA helicase answered the fundamental question of its enzymatic identity, placing it among the first characterized mammalian DEAD-box proteins.

    Evidence In vitro ATPase and RNA unwinding assays with purified/immunopurified human p68

    PMID:2471939 PMID:2527746

    Open questions at the time
    • Substrate specificity in vivo unknown
    • No structural information on how DDX5 engages RNA duplexes
    • Physiological function not yet defined
  2. 1991 High

    Observing dynamic cell-cycle-dependent relocalization of DDX5 (including translocation to prenucleolar bodies at telophase) and essentiality of the yeast ortholog established that DDX5 is not merely an enzymatic curiosity but a cell-essential factor with regulated subcellular behavior.

    Evidence Immunofluorescence microscopy across cell cycle; yeast deletion lethal phenotype

    PMID:1996094

    Open questions at the time
    • Mechanism of relocalization unknown
    • Specific essential function not identified
  3. 2001 High

    Demonstrating that DDX5 and its paralog DDX17 possess both RNA unwinding and RNA annealing activities via branch migration intermediates redefined DDX5 as an RNA chaperone rather than a simple helicase.

    Evidence In vitro helicase and annealing assays with recombinant DDX5/DDX17; ATP hydrolysis dependence

    PMID:11353078

    Open questions at the time
    • In vivo RNA substrates for annealing unknown
    • Relative contribution of unwinding vs. annealing to cellular phenotypes unclear
  4. 2003 High

    Identifying DDX5 as a regulator of c-H-ras alternative splicing and showing it forms heterodimers with DDX17 in large complexes established that DDX5 functions in pre-mRNA splicing regulation and operates as part of multi-subunit RNP assemblies.

    Evidence RNA affinity pulldown; RNAi with RT-PCR splicing readout; reciprocal co-IP; gel filtration

    PMID:12595555 PMID:12665590

    Open questions at the time
    • Genome-wide splicing targets unknown
    • How DDX5 is recruited to specific pre-mRNAs unclear
  5. 2005 High

    Showing that DDX5 coactivates p53-dependent transcription (recruited to the p21 promoter) and that its ATPase activity is specifically required for U1 snRNP displacement during splicing revealed DDX5 as a dual-function factor operating in both transcription and splicing through distinct mechanisms.

    Evidence Co-IP of endogenous DDX5-p53; ChIP at p21 promoter; RNAi reducing p53 target genes and apoptosis; in vitro splicing with ATPase-dead mutants

    PMID:15660129 PMID:16107697

    Open questions at the time
    • Whether transcriptional and splicing roles are mechanistically coupled unknown
    • Structural basis of p53 interaction undefined
  6. 2006 High

    Drosophila p68 mutants established a conserved role in mRNP export from transcription sites and in transcriptional deactivation by clearing RNA from chromatin, linking helicase activity to RNA trafficking.

    Evidence Drosophila genetics; FISH for hsp70 mRNA; phenocopy of NXF1 mutants

    PMID:16598038

    Open questions at the time
    • Whether mammalian DDX5 has identical export role not directly shown
    • Mechanism of RNA clearance from chromatin undefined
  7. 2007 High

    Discovery of SUMO-2 modification at K53 by PIAS1 and DDX5's role as a β-catenin transcriptional coactivator revealed how post-translational modifications toggle DDX5 between coactivation and corepression, and broadened its transcription factor partner repertoire.

    Evidence In vivo sumoylation with K53R mutant; HDAC1 recruitment assay; co-IP of DDX5-β-catenin; RNAi reducing β-catenin target genes

    PMID:17369852 PMID:17699760

    Open questions at the time
    • SUMO-dependent interactome not mapped
    • How sumoylation switches coactivation to corepression structurally unclear
  8. 2010 High

    Identification of p300-mediated acetylation (enhancing stability and ERα coactivation) and Y593 phosphorylation (promoting HDAC1 dissociation from Snail1 promoter via NuRD complex interaction) established that multiple PTMs fine-tune DDX5 transcriptional output at distinct promoters.

    Evidence In vitro acetyltransferase assay; site-directed mutagenesis of Y593; ChIP; co-IP with NuRD components

    PMID:20663877 PMID:20676135

    Open questions at the time
    • Complete PTM landscape not mapped
    • Crosstalk between acetylation, phosphorylation, and sumoylation not addressed
  9. 2011 High

    Mechanistic studies of tau exon 10 splicing and CUG repeat remodeling showed that DDX5 helicase activity restructures cis-regulatory RNA elements to modulate splicing factor access (U1 snRNP and MBNL1), connecting DDX5 to neurodegenerative disease-related RNA processing.

    Evidence RNA structural assays with helicase-dead mutants; U1 protection assays; MBNL1 binding assays; co-localization with CUG foci in DM1 cells

    PMID:21343338 PMID:22156369

    Open questions at the time
    • Whether DDX5 modulation alters DM1 disease progression in vivo untested
    • Full scope of DDX5-dependent splicing in neurons undefined
  10. 2013 High

    Genome-wide RNA-seq after DDX5/DDX17 knockdown and ChIP at AR-responsive promoters showed DDX5 is a master regulator of hormone receptor signaling pathways, controlling both transcription and splicing upstream and downstream of ER/AR.

    Evidence RNAi; RNA-seq; ChIP at PSA and other androgen-responsive loci; reporter assays

    PMID:23349811 PMID:24275493

    Open questions at the time
    • Direct versus indirect transcriptional targets not fully disentangled
    • Mechanism of DDX5 recruitment to AR/ER complexes not structurally resolved
  11. 2015 High

    Multiple discoveries in 2015 expanded DDX5's roles to include: (i) coactivation of RORγt in TH17 cells via lncRNA Rmrp-dependent interaction, (ii) Drosha/Microprocessor-mediated miRNA processing regulation, (iii) STAT3 coactivation, and (iv) AKT promoter activation with β-catenin/NF-κB, establishing DDX5 as a hub connecting transcription, miRNA biogenesis, and signaling.

    Evidence Co-IP of DDX5-RORγt (helicase-dead and Rmrp-mutant mice); co-IP of DDX5-Drosha with miRNA processing assays; ChIP at STAT3 and AKT target promoters; in vivo tumor models

    PMID:25745998 PMID:25963660 PMID:26675721 PMID:27941883

    Open questions at the time
    • How lncRNA Rmrp mediates DDX5-RORγt interaction structurally is unknown
    • Selectivity of DDX5 for specific pri-miRNA substrates not fully defined
  12. 2019 High

    Reconstitution of DDX5-mediated R-loop resolution and G-quadruplex unfolding, together with identification of PRMT5-dependent arginine methylation as required for XRN2 recruitment, redefined DDX5 as a genome integrity factor that resolves non-canonical nucleic acid structures.

    Evidence In vitro R-loop resolution with recombinant DDX5; DRIP-qPCR; γH2AX foci in DDX5 KO cells; in vitro G4-unfolding assays (ATP-independent); ChIP-seq at G-rich loci; PRMT5 methylation and XRN2 co-IP

    PMID:31267554 PMID:31548374

    Open questions at the time
    • Genome-wide map of DDX5-resolved R-loops not established
    • How DDX5 unfolds G4 without ATP hydrolysis structurally unexplained
    • Relative in vivo contribution of R-loop vs. G4 resolution to genome stability unknown
  13. 2019 High

    Inducible Ddx5 knockout in mouse spermatogonia caused male infertility, demonstrating an essential in vivo role in germline maintenance through splicing regulation of spermatogenesis genes and interaction with the transcription factor PLZF.

    Evidence Inducible KO mouse; RNA-seq splicing analysis; co-IP with PLZF

    PMID:31123254

    Open questions at the time
    • Which specific splicing events are causally linked to spermatogonial loss unclear
    • Redundancy with DDX17 in germline not addressed
  14. 2021 High

    DDX5 was shown to interact with METTL3 to promote m6A modification and nuclear export of innate immune transcripts, and with YTHDC1 to drive circRNA biogenesis, connecting DDX5 to epitranscriptomic regulation and back-splicing.

    Evidence Co-IP of DDX5-METTL3; m6A-seq; RNA export assays; co-IP of DDX5-YTHDC1; circRNA profiling by RNA-seq

    PMID:33909701 PMID:37019933

    Open questions at the time
    • Whether DDX5 helicase activity is required for m6A deposition unknown
    • Selectivity mechanism for circRNA vs. linear mRNA substrates unclear
  15. 2022 High

    Epistasis between DDX5 and TOP3B in R-loop resolution, and the discovery that DDX5 loss leads to IL-36R alternative splicing favoring membrane-bound isoform and cutaneous inflammation, extended DDX5's genome maintenance role and directly tied its splicing activity to inflammatory disease pathogenesis.

    Evidence IP-MS of TOP3B-DDX5; DRIP-seq in TOP3B KO cells; keratinocyte-specific Ddx5 KO mice with atopic dermatitis/psoriasis models; splicing analysis of IL-36R

    PMID:35830799 PMID:36271146

    Open questions at the time
    • Whether TOP3B-DDX5 complex is constitutive or signal-regulated unknown
    • How DDX5 loss is selective for IL-36R splicing among thousands of targets unclear
  16. 2023 High

    Conditional T cell-specific Ddx5 deletion revealed that DDX5 acts as a transcriptional corepressor of HIF1α in RORγt+ Tregs, restricting IL-10 and modulating intestinal inflammation, demonstrating that DDX5 can function as a corepressor to tune immune homeostasis.

    Evidence T cell-specific KO mice; ChIP; in vivo colitis models; HIF1α epistasis experiments

    PMID:36724232

    Open questions at the time
    • Mechanism by which DDX5 represses HIF1α transcription (cofactor identity) not defined
    • Whether corepressor function requires helicase activity unknown
  17. 2024 High

    Chondrocyte-specific Ddx5 deletion worsened osteoarthritis by disrupting both G-quadruplex-dependent Col2 transcription and alternative splicing of fibrosis genes (Fn1, Plod2), unifying DDX5's G4-resolving and splicing functions in a single disease-relevant tissue.

    Evidence Chondrocyte-specific conditional KO mice; in vitro G4-unfolding of Col2 promoter; RNA splicing analysis; OA mouse model

    PMID:38760576

    Open questions at the time
    • Whether pharmacological G4-stabilizers phenocopy Ddx5 KO in cartilage unknown
    • Contribution of DDX5's R-loop resolution activity to chondrocyte homeostasis untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A structural understanding of how DDX5 recognizes and resolves G-quadruplexes without ATP hydrolysis, the rules governing its context-dependent switch between coactivation and corepression, and the integrated logic by which PTMs (sumoylation, acetylation, methylation, phosphorylation, O-GlcNAcylation) coordinate its multifunctional outputs remain unresolved.
  • No high-resolution structure of DDX5 bound to G4 or R-loop substrates
  • Integrated PTM code governing partner selection not systematically mapped
  • Redundancy versus specialization relative to DDX17 not fully resolved across tissues

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003723 RNA binding 7 GO:0140098 catalytic activity, acting on RNA 6 GO:0140657 ATP-dependent activity 5 GO:0016787 hydrolase activity 4 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 3 GO:0005694 chromosome 2 GO:0005730 nucleolus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 12 R-HSA-8953854 Metabolism of RNA 12 R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 4 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 2
Partners
CTNNB1DDX17DROSHAMETTL3PRMT5TOP3BXRN2YTHDC1
Complex memberships
DDX5/DDX17 heterodimerDrosha/MicroprocessorMBD3/NuRD

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 Purified human p68 (DDX5) exhibits RNA-dependent ATPase activity and functions as an RNA helicase in vitro, unwinding RNA duplexes. In vitro RNA helicase and ATPase assays with purified protein Nature High 2471939
1989 Immunopurified human p68 (DDX5) has RNA-dependent ATPase activity; the protein undergoes dramatic changes in cellular localization during the cell cycle. Immunopurification followed by ATPase assay; immunofluorescence microscopy across cell cycle stages The EMBO journal High 2527746
1991 During telophase, mammalian p68 (DDX5), which is excluded from nucleoli during interphase, translocates to prenucleolar bodies; yeast orthologs are essential for cell viability. Immunofluorescent microscopy; yeast genetics (essential gene deletion) Molecular and cellular biology High 1996094
2001 Recombinant p68 (DDX5) and p72 (DDX17) possess both RNA helicase and RNA annealing activities; they catalyse RNA secondary structure rearrangements via branch migration intermediates in an ATP-hydrolysis-dependent manner. In vitro helicase and annealing assays with recombinant proteins; ATP hydrolysis-dependence experiments Nucleic acids research High 11353078
2001 p68 (DDX5) protein is poly-ubiquitylated in colorectal tumors and in cultured cells, suggesting regulation via the ubiquitin-proteasome pathway. Western blotting and immunohistochemistry of tumor specimens; ubiquitylation assays in cultured cells Oncogene Medium 11753651
2003 p68 (DDX5) and p72 (DDX17) preferentially exist as heterodimers in cells, can self-associate, and p68 also interacts with NFAR-2; gel filtration shows p68/p72 exist in complexes ranging from ~150 kDa to >2 MDa. Yeast two-hybrid; co-immunoprecipitation; gel filtration analysis Nucleic acids research High 12595555
2003 p68 (DDX5) RNA helicase binds both the alternative exon IDX and the intronic silencer rasISS1 of c-H-ras pre-mRNA and promotes IDX exclusion; RNAi knockdown of p68 increases IDX inclusion, establishing a role in alternative splicing regulation. RNA affinity pulldown; RNAi knockdown with RT-PCR splicing readout Molecular and cellular biology High 12665590
2005 p68 (DDX5) potently synergises with p53 to stimulate transcription from p53-dependent promoters; endogenous p68 and p53 co-immunoprecipitate from nuclear extracts; RNAi suppression of p68 inhibits p53 target gene expression after DNA damage and p53-dependent apoptosis; p68 is recruited to the p21 promoter in a p53-dependent manner (ChIP). Co-immunoprecipitation; RNAi knockdown with luciferase reporter and RT-PCR; chromatin immunoprecipitation (ChIP); apoptosis assays The EMBO journal High 15660129
2005 ATPase/helicase activities of p68 (DDX5) are required for its function in pre-mRNA splicing (specifically dissociation of U1 snRNA from the 5' splice site), but not for spliceosome assembly; ATPase-dead mutants (motif V and VI) abolish splicing function while still allowing prespliceosome-to-spliceosome transition. In vitro ATPase and RNA unwinding assays with helicase-dead mutants; in vitro splicing assays; RNAi in vivo Molecular and cellular biology High 16107697
2006 Drosophila p68 (ortholog of mammalian DDX5) promotes RNA export from transcription sites and facilitates transcriptional deactivation by clearing RNA from chromatin after heat shock; p68 mutations phenocopy mutations in the mRNA export factor NXF1/sbr. Drosophila genetics; fluorescence in situ hybridization for hsp70 mRNA; position effect variegation suppression assay Genes & development High 16598038
2007 p68 (DDX5) and p72 form complexes with β-catenin and promote β-catenin-dependent transcription of c-Myc, cyclin D1, c-jun, and fra-1; simultaneous knockdown of p68 and p72 reduces expression of these β-catenin-regulated genes and inhibits colon cancer cell proliferation. Co-immunoprecipitation; RNAi knockdown with RT-PCR and western blot; in vivo tumor formation assay Cancer research High 17699760
2007 p68 (DDX5) is modified by SUMO-2 on a single site (K53) in vivo; PIAS1 (SUMO E3 ligase) interacts with p68 and enhances its sumoylation; SUMO modification enhances p68 transcriptional repression activity, inhibits its p53 coactivator function, and promotes HDAC1 recruitment. In vivo sumoylation assay; co-immunoprecipitation; site-directed mutagenesis (K53R); transcriptional reporter assays; HDAC1 recruitment assay Oncogene High 17369852
2008 p68 (DDX5) interacts with Runx2 and functions as a transcriptional co-activator of Runx2; helicase activity is not essential for co-activation; p68 co-localizes with Runx2 in nuclear foci; knockdown of p68 mutes Runx2 transcriptional activity and accelerates osteoblast differentiation. Affinity purification/proteomics; co-immunoprecipitation; transcription reporter assays with helicase-dead mutant; RNAi knockdown; osteoblast differentiation assay Journal of cellular biochemistry High 17960593
2009 p68 (DDX5) shuttles between the nucleus and cytoplasm via two nuclear localization signals and two nuclear export signals, using a classical RanGTPase-dependent pathway. Subcellular fractionation; leptomycin B treatment; mutational analysis of NLS/NES; RanGTPase pathway inhibition Cell research High 19786986
2010 p68 (DDX5) and p72 (DDX17) are substrates for the acetyltransferase p300 in vitro and in vivo; acetylation increases their stability, stimulates their ability to coactivate estrogen receptor, and affects binding to histone deacetylases. In vitro acetyltransferase assay; co-immunoprecipitation; mutagenesis of acetylation sites; stability assays; reporter assays The Journal of biological chemistry High 20663877
2010 Tyrosine phosphorylation of p68 (DDX5) at Y593 activates transcription of the Snail1 gene by promoting dissociation of HDAC1 from the Snail1 promoter; p68 interacts with the MBD3:Mi-2/NuRD chromatin-remodeling complex. Site-directed mutagenesis (Y593); ChIP; co-immunoprecipitation with NuRD complex components; transcriptional reporter assays Oncogene High 20676135
2011 p68 (DDX5) identifies and remodels a stem-loop structure at the 5' splice site of tau exon 10 to increase access of U1 snRNP, thereby promoting tau exon 10 inclusion; this activity depends on helicase activity and functional interaction with RBM4. RNA affinity pulldown coupled mass spectrometry; RNase H cleavage and U1 protection assays; RNAi knockdown; helicase-dead mutant analysis Molecular and cellular biology High 21343338
2011 p68 (DDX5) colocalizes with CUG repeat RNA foci in DM1 cells; through its helicase activity, p68 remodels RNA secondary structure to facilitate MBNL1 binding to pathological CUG repeats and to the TNNT2 splicing regulatory element, thereby modifying MBNL1 splicing activity. Immunofluorescence co-localization; helicase-dead mutant analysis; MBNL1 binding assays; in vivo splicing assays Nucleic acids research High 22156369
2012 DDX5 and DDX17 act as transcriptional coactivators of NFAT5 and also regulate NFAT5 alternative splicing to include exon 5, which contains a premature stop codon, triggering NMD and reducing NFAT5 protein levels; knockdown of DDX5/DDX17 reduces tumor cell migration. RNAi knockdown; reporter assays; RT-PCR splicing analysis; cell migration assays Oncogene High 22266867
2012 DDX5 and DDX3 interact physically (mediated partly by dephosphorylation of serine/threonine residues), co-localize in cytoplasm especially in G2/M phase, and cooperate in mRNP export; DDX3 knockdown blocks nuclear shuttling of DDX5. Yeast two-hybrid; co-immunoprecipitation; GST pulldown; immunofluorescence; UV cross-linking; cell cycle fractionation; phosphatase treatment Journal of cellular biochemistry High 22034099
2013 DDX5 acts as a transcriptional co-activator of the androgen receptor (AR) in prostate cancer; it forms a complex with β-catenin in the nucleus in an androgen-dependent manner; ChIP shows p68 is recruited to androgen-responsive promoters and to elongating regions of the PSA gene, suggesting a role in facilitating RNA polymerase II elongation. Co-immunoprecipitation; chromatin immunoprecipitation (ChIP); luciferase reporter assays PloS one High 23349811
2013 DDX5 and DDX17 are master regulators of the estrogen- and androgen-signaling pathways, controlling transcription and splicing both upstream and downstream of ER and AR, including alternative splicing of GSK3β kinase which impacts ER and AR protein stability. RNAi knockdown; RNA-seq; RT-PCR; transcriptional reporter assays Nucleic acids research High 24275493
2014 DDX5 interacts with c-Myc and is required for c-Myc-mediated transcription and transforming activity; c-Myc overexpression increases DDX5 protein via accelerated synthesis, forming an oncogenic positive feedback loop; ARF disrupts the DDX5-c-Myc interaction and evicts DDX5 from c-Myc target gene promoters. Tandem affinity purification; co-immunoprecipitation; ChIP; transcription reporter assays; protein synthesis rate analysis Oncogene High 24469041
2015 DDX5 is a RORγt partner in TH17 cells; DDX5 coordinates transcription of selective TH17 genes and requires intrinsic RNA helicase activity and binding of the lncRNA Rmrp to interact with RORγt and coactivate its targets; a targeted Rmrp mutation in mice reduces DDX5-RORγt interaction and RORγt target gene transcription. Co-immunoprecipitation; genetic mouse models; lncRNA binding assays; helicase-dead mutant analysis; ChIP Nature High 26675721
2015 p68 (DDX5) functions as a transcriptional coactivator of STAT3; p68 directly interacts with STAT3, co-occupies promoters of STAT3 target genes (e.g., Mcl-1), and positively modulates STAT3 target gene mRNA and protein levels. Co-immunoprecipitation; ChIP; transcriptional reporter assays; RNAi knockdown; RT-PCR and western blot Oncogene High 27941883
2015 p68 (DDX5) co-activates AKT transcription in colon cancer by occupying the AKT promoter together with β-catenin and NF-κB; p68 knockdown reduces AKT mRNA and protein and diminishes AKT promoter activity; elevated AKT leads to FOXO3a nuclear exclusion and degradation. ChIP; luciferase reporter assays; RNAi knockdown; in vivo tumor model Oncogene High 25745998
2015 COX-2 increases DDX5 levels through PI3K/p300 signaling; DDX5 physically associates with Drosha (RNase III) complex to modulate its enzymatic function and repress miR-23b, miR-146b, and miR-183 processing in liver cells. Co-immunoprecipitation; RNAi knockdown; miRNA processing assays; luciferase reporter assays Molecular and cellular biology High 25963660
2015 LMTK3 binds DDX5 and sequesters pri-miRNAs of miR-34a, miR-196-a2, and miR-182 from further processing by the Microprocessor complex via DDX5, thereby regulating miRNA biogenesis. Co-immunoprecipitation; pri-miRNA binding assays; miRNA expression profiling; functional proliferation and invasion assays Cancer letters Medium 26739063
2017 DDX5 directly interacts with HDGF and induces β-catenin-c-Myc signaling; co-immunoprecipitation combined with mass spectrometry and GST pull-down confirmed formation of an HDGF/DDX5/β-catenin complex. Co-immunoprecipitation with mass spectrometry; GST pull-down; western blotting Clinical cancer research Medium 28751441
2017 Human DDX5 possesses ~10-fold higher RNA unwinding activity than its yeast ortholog Dbp2, partly due to a mammalian/avian-specific C-terminal extension; DDX5 rescues dbp2Δ yeast defects in cold sensitivity, cryptic transcription initiation, and glucose import, demonstrating functional conservation; DDX5 promotes glucose uptake and glycolysis in mouse hepatocytes. In vitro helicase assays; yeast complementation; glucose uptake assays in mammalian cells; mutant analysis RNA High 28411202
2018 O-GlcNAcylation of DDX5 by OGT promotes DDX5 protein stability; DDX5 directly interacts with OGT; OGT-mediated O-GlcNAcylation stabilizes DDX5 and promotes activation of the AKT/mTOR signaling pathway. Co-immunoprecipitation; western blotting; OGT knockdown/inhibition assays Journal of cellular and molecular medicine Medium 30484950
2019 DDX5 resolves R-loops in vitro in an ATP-dependent manner, leading to R-loop RNA degradation by XRN2; DDX5-deficient cells accumulate R-loops and exhibit spontaneous DNA double-strand breaks and replication stress hypersensitivity; PRMT5 binds and methylates DDX5 at its RGG/RG motif, which is required for DDX5-XRN2 interaction and cellular R-loop repression but not for helicase enzymatic activity per se. In vitro R-loop resolution assay with recombinant DDX5; DRIP-qPCR; γH2AX foci counting; co-immunoprecipitation; arginine methylation assay; DDX5 knockout cell lines The EMBO journal High 31267554
2019 DDX5 is a highly active G4-resolvase that unfolds MYC promoter G-quadruplex DNA (MycG4) without requiring a single-stranded DNA overhang and independent of ATP hydrolysis; DDX5 is enriched at G-rich chromatin sites including the MYC promoter and activates MYC transcription; G4-interactive small molecules inhibit DDX5-MYC promoter interaction. In vitro G4-unfolding assays; ChIP-seq; transcription reporter assays; ATP hydrolysis mutant analysis; small molecule inhibition Proceedings of the National Academy of Sciences High 31548374
2019 DDX5 interacts with PLZF (a transcription factor required for germline maintenance) and co-regulates select target genes; DDX5 regulates splicing of key spermatogenesis genes and post-transcriptionally controls cell cycle gene expression; inducible Ddx5 knockout in mice causes spermatogonial loss and male infertility. Inducible knockout mouse model; co-immunoprecipitation; RNA-seq splicing analysis; cell proliferation and survival assays Nature communications High 31123254
2019 DDX5 interacts with the JEV core protein, NS3, and NS5 viral proteins and with JEV 3' UTR RNA; DDX5 is recruited to the cytoplasm and colocalizes with viral proteins and RNA during infection; DDX5 helicase activity is required for JEV replication. GST pulldown; co-immunoprecipitation; confocal microscopy; RNA pulldown; helicase-dead mutant analysis; JEV replicon system Antiviral research High 24035833
2019 LNCERNA CCAT1 acts as a scaffold for DDX5 and the androgen receptor transcriptional complex in the nucleus, facilitating AR-regulated gene expression and CRPC progression; in the cytoplasm, CCAT1 sponges miR-28-5P. RNA immunoprecipitation; co-immunoprecipitation; nuclear/cytoplasmic fractionation; reporter assays Molecular cancer therapeutics Medium 31387890
2020 DDX5 resolves the G-quadruplex structure in the 5' UTR of STAT1 mRNA to enable STAT1 translation; direct and selective binding of helicase-active DDX5 to WT STAT1-rG4 sequence demonstrated by RNP and EMSA assays; CRISPR editing of STAT1-rG4 sequence confers resistance to rG4-stabilising compounds. Luciferase reporter assays; CRISPR/Cas9 gene editing; circular dichroism; RNP assay; EMSA; rG4-stabilising compound treatment Gut High 34021034
2021 DDX5 interacts with the m6A writer METTL3, affects METTL3-METTL14 heterodimer complex formation, and promotes m6A modification and nuclear export of DHX58, p65, and IKKγ transcripts via binding to a conserved UGCUGCAG element, dampening antiviral innate immunity. Co-immunoprecipitation; m6A sequencing; RNA pulldown; nuclear export assays; reporter assays; in vivo viral infection model PLoS pathogens High 33909701
2021 Thrap3 interacts with arginine-methylated DDX5 (methylation required for interaction); the Thrap3-DDX5 axis recruits XRN2 to R-loops; loss of Thrap3 increases R-loop accumulation and DNA damage. Co-immunoprecipitation; methylation assays; R-loop immunofluorescence; DNA damage marker analysis Experimental & molecular medicine Medium 34697388
2022 TOP3B interacts with DDX5 independently of TDRD3; DDX3 is physically associated with R-loops; TOP3B cleaves displaced ssDNA in R-loop structures; TOP3B and DDX5 are epistatic in R-loop resolution in a pathway parallel to senataxin. IP-mass spectrometry; IP-western blotting; biochemical R-loop cleavage assay with recombinant proteins; DRIP-seq; TOP3B knockout cells Cell reports High 35830799
2022 IL-17D inhibits DDX5 expression in keratinocytes through the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway; loss of DDX5 leads to alternative splicing favoring membrane-bound over soluble IL-36R, amplifying IL-36R-mediated inflammation; keratinocyte-specific Ddx5 knockout mice are more susceptible to cutaneous inflammation. Keratinocyte-specific conditional knockout mice; RNA splicing analysis; cytokine signaling pathway dissection; in vivo atopic dermatitis and psoriasis models Nature immunology High 36271146
2023 DDX5 interacts with the m6A reader YTHDC1; both DDX5 and YTHDC1 promote back-splicing to produce a common subset of circRNAs in rhabdomyosarcoma; depletion of DDX5 or YTHDC1 reduces circRNA production and RMS proliferation. Co-immunoprecipitation; RNA-seq for circRNA profiling; RNAi knockdown; proliferation assays Nature communications High 37019933
2023 As a transcriptional corepressor in RORγt+ Tregs, DDX5 restricts HIF1α expression and the HIF1α target gene Il10; T cell-specific Ddx5 knockout enhances RORγt+ Treg suppressor activity and IL-10 production, protecting mice from intestinal inflammation. T cell-specific conditional knockout mice; ChIP; gene expression analysis; in vivo colitis models; HIF1α genetic and pharmacological inhibition as epistasis Science advances High 36724232
2024 DDX5 inhibits hyaline cartilage fibrosis by (1) regulating alternative splicing of Fn1 and Plod2 to suppress fibrosis-related genes (Col1, Acta2) and ECM-degrading enzymes (Mmp13, Nos2); and (2) unfolding the Col2 promoter G-quadruplex to maintain COL2 expression; chondrocyte-specific Ddx5 deletion worsens cartilage lesions in OA mice. Chondrocyte-specific conditional knockout mice; in vitro G4-unfolding assays; RNA splicing analysis; OA mouse model Nature aging High 38760576

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. Journal of hematology & oncology 322 30185232
1992 Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. The EMBO journal 319 1348691
1989 RNA helicase activity associated with the human p68 protein. Nature 289 2471939
2005 The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. The EMBO journal 199 15660129
2007 Involvement of RNA helicases p68 and p72 in colon cancer. Cancer research 161 17699760
2019 Arginine methylation of the DDX5 helicase RGG/RG motif by PRMT5 regulates resolution of RNA:DNA hybrids. The EMBO journal 146 31267554
2015 DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature 138 26675721
1989 Nuclear protein p68 is an RNA-dependent ATPase. The EMBO journal 133 2527746
2013 The DEAD box proteins DDX5 (p68) and DDX17 (p72): multi-tasking transcriptional regulators. Biochimica et biophysica acta 127 23523990
2001 Overexpression and poly-ubiquitylation of the DEAD-box RNA helicase p68 in colorectal tumours. Oncogene 127 11753651
1991 p68 RNA helicase: identification of a nucleolar form and cloning of related genes containing a conserved intron in yeasts. Molecular and cellular biology 125 1996094
2018 African swine fever virus (ASFV) protection mediated by NH/P68 and NH/P68 recombinant live-attenuated viruses. Vaccine 124 29609966
2003 Roles of hnRNP A1, SR proteins, and p68 helicase in c-H-ras alternative splicing regulation. Molecular and cellular biology 113 12665590
2019 DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia. Nature communications 108 31123254
2011 RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5' splice site. Molecular and cellular biology 104 21343338
2019 DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation. Proceedings of the National Academy of Sciences of the United States of America 102 31548374
2011 RNA helicases p68 and p72: multifunctional proteins with important implications for cancer development. Future oncology (London, England) 97 21345143
2018 The DDX5/Dbp2 subfamily of DEAD-box RNA helicases. Wiley interdisciplinary reviews. RNA 95 30506978
1996 p72: a human nuclear DEAD box protein highly related to p68. Nucleic acids research 95 8871553
2008 The DEAD box RNA helicases p68 (Ddx5) and p72 (Ddx17): novel transcriptional co-regulators. Biochemical Society transactions 93 18631126
2001 Rearrangement of structured RNA via branch migration structures catalysed by the highly related DEAD-box proteins p68 and p72. Nucleic acids research 87 11353078
2017 miRomics and Proteomics Reveal a miR-296-3p/PRKCA/FAK/Ras/c-Myc Feedback Loop Modulated by HDGF/DDX5/β-catenin Complex in Lung Adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 86 28751441
2019 LncRNA CCAT1 Promotes Prostate Cancer Cell Proliferation by Interacting with DDX5 and MIR-28-5P. Molecular cancer therapeutics 82 31387890
2018 Roles of DDX5 in the tumorigenesis, proliferation, differentiation, metastasis and pathway regulation of human malignancies. Biochimica et biophysica acta. Reviews on cancer 75 30419318
2003 The highly related DEAD box RNA helicases p68 and p72 exist as heterodimers in cells. Nucleic acids research 73 12595555
2022 IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation. Nature immunology 70 36271146
2020 LncRNA SLC26A4-AS1 suppresses the MRN complex-mediated DNA repair signaling and thyroid cancer metastasis by destabilizing DDX5. Oncogene 70 32939012
2007 SUMO modification of the DEAD box protein p68 modulates its transcriptional activity and promotes its interaction with HDAC1. Oncogene 68 17369852
2002 Identification and functional characterization of the p66/p68 components of the MeCP1 complex. Molecular and cellular biology 68 11756549
2011 New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats. Nucleic acids research 66 22156369
2008 p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. Journal of cellular biochemistry 66 17960593
2006 The Drosophila P68 RNA helicase regulates transcriptional deactivation by promoting RNA release from chromatin. Genes & development 64 16598038
2022 DDX5 and DDX17-multifaceted proteins in the regulation of tumorigenesis and tumor progression. Frontiers in oncology 63 35992805
1984 Cellular distribution of p68, a new calcium-binding protein from lymphocytes. The EMBO journal 63 6376118
2005 ATPase/helicase activities of p68 RNA helicase are required for pre-mRNA splicing but not for assembly of the spliceosome. Molecular and cellular biology 62 16107697
2012 Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor. Oncogene 61 22266867
2003 Complete nucleotide sequence and molecular characterization of two lytic Staphylococcus aureus phages: 44AHJD and P68. FEMS microbiology letters 60 12620632
2022 Resolution of R-loops by topoisomerase III-β (TOP3B) in coordination with the DEAD-box helicase DDX5. Cell reports 59 35830799
2019 Structure and genome ejection mechanism of Staphylococcus aureus phage P68. Science advances 59 31663016
2013 The DEAD-box RNA helicase DDX5 acts as a positive regulator of Japanese encephalitis virus replication by binding to viral 3' UTR. Antiviral research 59 24035833
2010 Pleiotropic effects of p300-mediated acetylation on p68 and p72 RNA helicase. The Journal of biological chemistry 59 20663877
2018 Coordinate regulation of alternative pre-mRNA splicing events by the human RNA chaperone proteins hnRNPA1 and DDX5. Genes & development 58 30042133
2015 The DEAD box protein p68: a crucial regulator of AKT/FOXO3a signaling axis in oncogenesis. Oncogene 58 25745998
2018 DDX5 RNA Helicases: Emerging Roles in Viral Infection. International journal of molecular sciences 57 29642538
2020 LINC01116 promotes tumor proliferation and neutrophil recruitment via DDX5-mediated regulation of IL-1β in glioma cell. Cell death & disease 56 32358484
2021 The RNA helicase DDX5 promotes viral infection via regulating N6-methyladenosine levels on the DHX58 and NFκB transcripts to dampen antiviral innate immunity. PLoS pathogens 55 33909701
2021 LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis. Theranostics 52 33754075
2018 The role of DEAD-box RNA helicase p68 (DDX5) in the development and treatment of breast cancer. Journal of cellular physiology 52 30417346
2021 RNA helicase DDX5 enables STAT1 mRNA translation and interferon signalling in hepatitis B virus replicating hepatocytes. Gut 49 34021034
2014 DEAD-box protein p68 is regulated by β-catenin/transcription factor 4 to maintain a positive feedback loop in control of breast cancer progression. Breast cancer research : BCR 49 25499975
1999 p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K. FEBS letters 49 10437794
2013 The Ddx5 and Ddx17 RNA helicases are cornerstones in the complex regulatory array of steroid hormone-signaling pathways. Nucleic acids research 48 24275493
2016 Resveratrol directly targets DDX5 resulting in suppression of the mTORC1 pathway in prostate cancer. Cell death & disease 46 27148684
1993 High-level expression in male germ cells of murine P68 RNA helicase mRNA. Life sciences 45 8445986
2018 O-GlcNAcylation promotes colorectal cancer progression by regulating protein stability and potential catcinogenic function of DDX5. Journal of cellular and molecular medicine 44 30484950
2009 P68 RNA helicase is a nucleocytoplasmic shuttling protein. Cell research 44 19786986
2020 Restoration of RNA helicase DDX5 suppresses hepatitis B virus (HBV) biosynthesis and Wnt signaling in HBV-related hepatocellular carcinoma. Theranostics 43 33042264
2012 The DEAD-box RNA helicase DDX3 interacts with DDX5, co-localizes with it in the cytoplasm during the G2/M phase of the cycle, and affects its shuttling during mRNP export. Journal of cellular biochemistry 43 22034099
2023 The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs. Nature communications 42 37019933
2017 Characterization of the mammalian DEAD-box protein DDX5 reveals functional conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and glucose metabolism. RNA (New York, N.Y.) 42 28411202
2001 Expression of p68 RNA helicase is closely related to the early stage of adipocyte differentiation of mouse 3T3-L1 cells. Biochemical and biophysical research communications 42 11554747
2014 P68 RNA helicase as a molecular target for cancer therapy. Journal of experimental & clinical cancer research : CR 40 25150365
2013 p68/DdX5 supports β-catenin & RNAP II during androgen receptor mediated transcription in prostate cancer. PloS one 40 23349811
2015 Regulation of MicroRNA 183 by Cyclooxygenase 2 in Liver Is DEAD-Box Helicase p68 (DDX5) Dependent: Role in Insulin Signaling. Molecular and cellular biology 39 25963660
2022 FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy. Clinical and translational medicine 36 35604033
2005 Phage P68 virion-associated protein 17 displays activity against clinical isolates of Staphylococcus aureus. Antimicrobial agents and chemotherapy 36 15980371
2010 Phosphorylated p68 RNA helicase activates Snail1 transcription by promoting HDAC1 dissociation from the Snail1 promoter. Oncogene 35 20676135
2014 Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5. Oncogene 34 24469041
2012 Forced expression of miR-143 represses ERK5/c-Myc and p68/p72 signaling in concert with miR-145 in gut tumors of Apc(Min) mice. PloS one 34 22876303
2023 Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence. Journal of experimental & clinical cancer research : CR 33 37596619
2019 Long noncoding RNA DLEU1 aggravates osteosarcoma carcinogenesis via regulating the miR-671-5p/DDX5 axis. Artificial cells, nanomedicine, and biotechnology 33 31379208
2018 miR-5590-3p inhibited tumor growth in gastric cancer by targeting DDX5/AKT/m-TOR pathway. Biochemical and biophysical research communications 33 30029874
2014 Acquired dependence of acute myeloid leukemia on the DEAD-box RNA helicase DDX5. Cell reports 33 24910429
2024 DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding. Nature aging 32 38760576
2020 Silencing of p68 and STAT3 synergistically diminishes cancer progression. Life sciences 32 32142763
2021 LncPSCA in the 8q24.3 risk locus drives gastric cancer through destabilizing DDX5. EMBO reports 31 34472665
2020 Long Noncoding RNA NHEG1 Drives β-Catenin Transactivation and Neuroblastoma Progression through Interacting with DDX5. Molecular therapy : the journal of the American Society of Gene Therapy 31 31982037
2019 Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin. Frontiers in oncology 30 31032220
2019 First-in-Class Phosphorylated-p68 Inhibitor RX-5902 Inhibits β-Catenin Signaling and Demonstrates Antitumor Activity in Triple-Negative Breast Cancer. Molecular cancer therapeutics 29 31488700
2018 DDX5 promotes hepatocellular carcinoma tumorigenesis via Akt signaling pathway. Biochemical and biophysical research communications 29 30119889
2015 LMTK3 escapes tumour suppressor miRNAs via sequestration of DDX5. Cancer letters 29 26739063
1996 Dual expression of p80 type I and p68 type II interleukin-I receptors on anterior pituitary cells synthesizing growth hormone. Endocrinology 29 8756580
2021 Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy. American journal of cancer research 28 34765320
2021 Thrap3 promotes R-loop resolution via interaction with methylated DDX5. Experimental & molecular medicine 27 34697388
2016 The DEAD box protein p68: a novel coactivator of Stat3 in mediating oncogenesis. Oncogene 26 27941883
2016 Knockdown of DDX5 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer. Oncology research 26 28244855
2020 Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis. Human cell 24 32920730
2000 p68, a DEAD-box RNA helicase, is expressed in chordate embryo neural and mesodermal tissues. The Journal of experimental zoology 23 11069138
1992 Expression of the protein kinase p-68 recognized by the monoclonal antibody TJ4C4 in human lung neoplasms. Virchows Archiv. B, Cell pathology including molecular pathology 23 1357815
1989 Chromosome mapping of the human gene encoding the 68-kDa nuclear antigen (p68) by using the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America 23 2762324
2021 LncRNA SNHG14 promotes cell proliferation and invasion in colorectal cancer through modulating miR-519b-3p/DDX5 axis. Journal of Cancer 22 34234865
2002 Role of the p68 subunit of human DNA polymerase alpha-primase in simian virus 40 DNA replication. Molecular and cellular biology 22 12138179
2023 AURKAIP1 actuates tumor progression through stabilizing DDX5 in triple negative breast cancer. Cell death & disease 21 38040691
2022 DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective. Cancers 21 35954483
2023 The feedback loop of AURKA/DDX5/TMEM147-AS1/let-7 drives lipophagy to induce cisplatin resistance in epithelial ovarian cancer. Cancer letters 20 37217070
2020 RNA helicase p68 inhibits the transcription and post-transcription of Pkd1 in ADPKD. Theranostics 20 32724471
2019 Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1. Oncogene 20 31015574
2010 Role of multiple HLR1 sequences in the regulation of the dual promoters of the psaAB genes in Synechocystis sp. PCC 6803. Journal of bacteriology 20 20511509
2023 RNA binding protein DDX5 restricts RORγt+ Treg suppressor function to promote intestine inflammation. Science advances 18 36724232
2021 Wnt/β-catenin signaling and p68 conjointly regulate CHIP in colorectal carcinoma. Biochimica et biophysica acta. Molecular cell research 18 34890713