Affinage

SEPTIN4

Septin-4 · UniProt O43236

Length
996 aa
Mass
112.4 kDa
Annotated
2026-04-28
100 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SEPTIN4 encodes two functionally distinct isoforms: Sept4_i1, a canonical septin that participates in cytokinesis and filament formation, and Sept4_i2 (ARTS), a mitochondrially localized pro-apoptotic protein that controls stem cell pool size and tissue homeostasis by promoting XIAP-dependent apoptosis (PMID:21824006, PMID:20952537, PMID:23788729, PMID:30389919). Upon apoptotic stimulation, ARTS is released from mitochondria and directly binds the BIR1 domain of XIAP, recruiting the E3 ligase Siah-1 to ubiquitinate and degrade XIAP; ARTS further assembles a ternary complex with XIAP and Bcl-2, enabling XIAP-mediated ubiquitination of Bcl-2 at Lys17 (PMID:15029247, PMID:21185211, PMID:29020630). ARTS itself is regulated by Parkin-mediated ubiquitination that keeps its basal levels low, by SIRT2-mediated deacetylation at K174 that restrains its apoptotic activity, and by p53-driven transcription that amplifies ARTS expression under genotoxic stress (PMID:22792159, PMID:36786216, PMID:33627621). Biallelic loss-of-function mutations in SEPTIN4 cause male infertility in humans by disrupting the septin-based annulus of spermatozoa (PMID:36135717).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 High

    Establishing the core pro-apoptotic mechanism of ARTS: the discovery that ARTS is released from mitochondria and directly binds XIAP to antagonize caspase inhibition resolved how a septin-family protein could function as an IAP antagonist, distinct from canonical Smac/DIABLO.

    Evidence In vitro binding of recombinant ARTS–XIAP, ARTS mutant analysis, Drosophila genetic epistasis

    PMID:15029247

    Open questions at the time
    • Precise ARTS residues mediating XIAP binding not mapped
    • Mechanism of mitochondrial release not defined
    • In vivo physiological role in mammals not yet tested
  2. 2005 Medium

    Demonstrating that ARTS protein abundance is constitutively restrained by ubiquitin-mediated degradation explained how cells keep the apoptotic trigger latent until needed, with stabilization upon stress leading to Bcl-2/Bcl-xL downregulation and cytochrome c release.

    Evidence Ubiquitination assays and proteasome inhibitor experiments in cell lines

    PMID:15837787

    Open questions at the time
    • Identity of the E3 ligase responsible not determined in this study
    • In vivo relevance of ARTS turnover not shown
  3. 2010 High

    Two advances defined how ARTS promotes XIAP destruction and revealed its physiological role in stem cells: ARTS was shown to bridge Siah-1 to XIAP for ubiquitin-dependent degradation via the BIR1 domain, and Sept4-knockout mice exhibited expanded hematopoietic stem/progenitor pools with elevated XIAP, a phenotype reversed by XIAP deletion.

    Evidence Co-IP domain mapping and knockdown/knockout XIAP level analysis; Sept4-null mice with XIAP genetic epistasis and Eμ-Myc tumor assay

    PMID:20952537 PMID:21185211

    Open questions at the time
    • Whether ARTS-Siah-1-XIAP ternary complex forms in primary stem cells not shown
    • Structural basis of BIR1 recognition undefined
  4. 2011 Medium

    Molecular characterization clarified that SEPT4 produces two structurally and functionally divergent isoforms — Sept4_i1 (canonical septin) and Sept4_i2 (ARTS, mitochondrial pro-apoptotic) — through alternative promoters and splicing, contextualizing why the same locus controls both cytokinesis and apoptosis.

    Evidence Isoform characterization, structural comparison, literature synthesis

    PMID:21824006

    Open questions at the time
    • Tissue-specific promoter usage not fully resolved
    • Relative expression levels of isoforms in different tissues poorly characterized
  5. 2012 Medium

    Identification of Parkin as the E3 ligase that selectively ubiquitinates and degrades ARTS (but not Sept4_i1) connected ARTS turnover to Parkinson's disease-relevant pathways and explained the isoform-specific degradation observed earlier.

    Evidence Co-IP, ubiquitination assays with Parkin overexpression/knockdown in neuronal cells

    PMID:22792159

    Open questions at the time
    • Parkin-ARTS interaction not validated in primary neurons or brain tissue
    • Specific ubiquitination sites on ARTS not identified
  6. 2013 High

    Extension of the ARTS–XIAP axis to hair follicle stem cells demonstrated that ARTS controls tissue-resident stem cell apoptosis in vivo, with Sept4-knockout mice showing enhanced wound healing and hair regeneration reversed by XIAP deletion.

    Evidence Sept4-knockout mice with lineage tracing, wound healing assays, XIAP genetic epistasis

    PMID:23788729

    Open questions at the time
    • Molecular signals triggering ARTS activation in the hair follicle niche unknown
    • Human relevance not tested
  7. 2017 High

    Discovery that ARTS assembles a ternary complex with XIAP and Bcl-2 to enable XIAP-mediated ubiquitination of Bcl-2 at K17 revealed a second anti-survival target beyond XIAP itself, showing ARTS amplifies apoptotic commitment by simultaneously degrading both an IAP and an anti-apoptotic Bcl-2 family member.

    Evidence Co-IP, ubiquitylation assays, K17A Bcl-2 mutant stability, XIAP and Sept4 knockout MEFs

    PMID:29020630

    Open questions at the time
    • Whether other Bcl-2 family members are similarly targeted unknown
    • Temporal order of XIAP versus Bcl-2 degradation not resolved
  8. 2018 High

    Demonstration that ARTS operates in the intestinal stem cell niche — protecting Lgr5+ and Paneth cells from apoptosis when deleted, and enhancing Wnt/β-catenin signaling — broadened its physiological role to gut homeostasis and showed the ARTS–XIAP axis is a general stem cell apoptosis regulator.

    Evidence Sept4-knockout mice, intestinal organoids, Co-IP of ARTS–XIAP in crypts, genetic epistasis with XIAP knockout

    PMID:30389919

    Open questions at the time
    • Whether ARTS loss predisposes to intestinal tumorigenesis long-term not fully addressed
    • Mechanism linking XIAP degradation to Wnt activation unclear
  9. 2020 Medium

    Identification of SEPTIN4 as a scaffold bridging SIRT1 and STAT3 to promote STAT3-K685 deacetylation and Y705 dephosphorylation revealed a non-apoptotic signaling function of SEPTIN4 in vascular smooth muscle cell phenotypic modulation.

    Evidence Co-IP of SEPTIN4–SIRT1–STAT3 complex, knockdown/overexpression in HAVSMCs with modification-specific immunoblotting

    PMID:32025217

    Open questions at the time
    • Which isoform mediates STAT3 regulation not specified
    • Single-lab finding without independent replication
    • Direct physical bridging not reconstituted with purified components
  10. 2021 Medium

    Establishing a positive feedback loop between p53 and ARTS — p53 transcriptionally activates ARTS, and ARTS in turn sequesters p53 at mitochondria to enhance p53–Bcl-XL interaction — linked the ARTS pathway to the canonical DNA damage response.

    Evidence ChIP on ARTS promoter, luciferase reporter, Co-IP of ARTS–p53, apoptosis assays with p53 manipulation

    PMID:33627621

    Open questions at the time
    • Physiological importance of p53–ARTS loop in stem cells or tumors not tested in vivo
    • Whether ARTS-mediated p53 mitochondrial sequestration is independent of XIAP pathway unclear
  11. 2022 Medium

    Human genetic evidence that biallelic SEPTIN4 loss-of-function causes male infertility through disrupted sperm annulus structure established a Mendelian disease link and confirmed the canonical septin isoform's structural role in spermatogenesis.

    Evidence Whole-exome sequencing of infertile patients, immunofluorescence and EM of sperm ultrastructure

    PMID:36135717

    Open questions at the time
    • Single study without independent cohort replication
    • Whether ARTS isoform loss contributes to any aspect of the infertility phenotype unknown
  12. 2023 High

    Identifying SIRT2-mediated deacetylation of SEPTIN4 at K174 as a regulatory switch — where hyperacetylation activates the caspase-3/PARP1 apoptotic pathway and exacerbates renal injury — added a post-translational regulatory layer controlling SEPTIN4's pro-apoptotic output.

    Evidence Acetyl-proteomics, Co-IP/MS, K174Q and K174R transgenic mice, SIRT2-knockout mice, podocyte injury models

    PMID:36786216

    Open questions at the time
    • Whether K174 acetylation affects ARTS–XIAP binding specifically not tested
    • Acetylation writers not identified
    • Relevance to stem cell apoptosis function not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of ARTS–XIAP BIR1 recognition, the mechanism by which ARTS is released from mitochondria, whether the ARTS–XIAP stem cell apoptosis axis is relevant in human cancer suppression, and how the two isoforms are differentially regulated at the transcriptional level across tissues.
  • No crystal or cryo-EM structure of ARTS or ARTS–XIAP complex
  • Mitochondrial release mechanism undefined
  • Human disease relevance of ARTS-mediated stem cell apoptosis not established beyond infertility

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 2
Pathway
R-HSA-5357801 Programmed Cell Death 9 R-HSA-392499 Metabolism of proteins 5
Partners
BCL2PRKNSIAH1SIRT1SIRT2STAT3TP53XIAP
Complex memberships
ARTS-XIAP-Bcl-2ARTS-XIAP-Siah-1

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 ARTS (SEPT4_i2), a mitochondrial septin-like protein, is released from mitochondria upon pro-apoptotic stimuli and directly binds XIAP to antagonize its caspase-inhibitory function, leading to decreased XIAP protein levels and caspase activation. Recombinant ARTS and XIAP bind each other in vitro, and ARTS mutants that fail to bind XIAP fail to induce apoptosis. In vitro binding assay with recombinant proteins, Co-immunoprecipitation, cell-based apoptosis assays with mutant ARTS, Drosophila genetic epistasis (peanut mutations suppress Reaper/Hid/Grim killing) The EMBO journal High 15029247
2010 ARTS binds XIAP at the BIR1 domain (distinct from caspase-binding sites) and interacts with the E3 ubiquitin ligase Siah-1, acting as an adaptor to bridge Siah-1 to XIAP and target it for ubiquitination and proteasomal degradation. Cells lacking either Siah or ARTS have elevated steady-state XIAP levels. Co-immunoprecipitation, domain mapping, knockdown/knockout cell lines with XIAP level measurement Molecular cell High 21185211
2017 ARTS forms a ternary complex with XIAP and Bcl-2, enabling XIAP to act as an E3 ligase that ubiquitinates Bcl-2 at Lys17, leading to its proteasomal degradation. ARTS binding to Bcl-2 involves the BH3 domain of Bcl-2. XIAP- and Sept4/ARTS-deficient MEFs both show reduced Bcl-2 ubiquitylation. Co-immunoprecipitation, ubiquitylation assays, K17A Bcl-2 mutant stability analysis, knockout MEFs Cell reports High 29020630
2010 Deletion of mouse Sept4 gene leads to increased numbers of hematopoietic stem and progenitor cells, elevated XIAP protein levels, increased resistance to apoptosis, and accelerated tumor development; these phenotypes are partially suppressed by XIAP inactivation, placing ARTS upstream of XIAP in stem cell apoptosis. Sept4-null mouse model, genetic epistasis with XIAP knockout, flow cytometry of hematopoietic progenitors, tumor development assay in Eμ-Myc background Genes & development High 20952537
2013 Sept4/ARTS-deficient mice have elevated numbers of hair follicle stem cells (HFSCs) protected against apoptosis, display improved wound healing and hair follicle regeneration; these phenotypes depend on HFSCs (shown by lineage tracing) and are abrogated by XIAP inactivation, demonstrating ARTS regulates stem cell apoptosis via XIAP. Sept4/ARTS knockout mice, lineage tracing, XIAP genetic inactivation, wound healing assay Science (New York, N.Y.) High 23788729
2005 In healthy cells, ARTS protein levels are kept low through constant ubiquitin-mediated proteasomal degradation; upon pro-apoptotic stimuli, ubiquitination is inhibited, ARTS levels rise, leading to decreased Bcl-2 and Bcl-xL levels, cytochrome c release, and apoptosis. Ubiquitination assays, proteasome inhibitor experiments, overexpression and knockdown in cell lines The Journal of biological chemistry Medium 15837787
2012 Parkin acts as an E3 ubiquitin ligase for ARTS (Sept4_i2), binding both ARTS and Sept4_i1 but selectively ubiquitinating and degrading only ARTS; Parkin overexpression protects neuronal cells from ARTS-induced apoptosis, and Parkin loss-of-function increases ARTS levels and promotes apoptosis. Co-immunoprecipitation, ubiquitination assays, Parkin overexpression/knockdown, neuronal cell apoptosis assays PloS one Medium 22792159
2021 ARTS is a transcriptional target of p53; p53 binds the ARTS promoter and activates its expression in response to genotoxic stress. In turn, ARTS binds p53 and sequesters it at mitochondria, enhancing p53 interaction with Bcl-XL to promote mitochondrial apoptosis. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, Co-immunoprecipitation, p53 ablation/ectopic expression, apoptosis assays Cell death & disease Medium 33627621
2011 The SEPT4 gene encodes two major isoforms via distinct promoters, differential splicing, and intron retention: Sept4_i1 (H5/PNUTL2), a canonical septin involved in cytokinesis and filament formation, and Sept4_i2 (ARTS), which localizes to mitochondria and promotes apoptosis — distinguishing ARTS structurally and functionally from all other human septins. Molecular characterization of isoforms, structural and functional comparison, literature synthesis Biological chemistry Medium 21824006
2023 SIRT2 deacetylates SEPTIN4 at lysine 174 (K174); hyperacetylation of K174 (mimicked by K174Q mutant) activates the cleaved-PARP1/cleaved-caspase3 apoptotic pathway and exacerbates Ang II-induced hypertensive renal injury in podocytes, while K174R (deacetylation mimic) is renoprotective. Immunoprecipitation and mass spectrometry identified SIRT2 as the deacetylase that interacts with the SEPTIN4 GTPase domain. Proteomics and acetyl-proteomics, Co-immunoprecipitation with mass spectrometry, transgenic K174Q and K174R mutant mice, SIRT2 knockout and transgenic mice, Western blotting Circulation research High 36786216
2018 ARTS (Septin4 isoform) is highly expressed in intestinal stem cell niche cells; deletion of Sept4/ARTS protects Lgr5+ and Paneth cells from apoptosis, enhances Wnt/β-catenin signaling, and generates resistance to intestinal damage; ARTS interacts with XIAP in intestinal crypt cells and XIAP deletion abrogates these phenotypes. Sept4/ARTS knockout mice, organoid culture, Co-immunoprecipitation of ARTS-XIAP in intestinal crypts, β-catenin signaling assays, genetic epistasis with XIAP knockout Nature communications High 30389919
2022 Biallelic loss-of-function variants in SEPTIN4 in human patients cause thin midpiece spermatozoa and male infertility by disrupting the septin-based annulus structure, impairing localization of SEPTIN subunits at the annulus, disorganizing the mitochondrial sheath, and causing mislocalisation of SLC26A8 (a testis-specific anion transporter that colocalizes with SEPT4 at the sperm annulus). Whole-exome sequencing, immunofluorescence, immunoblotting, ultrastructural electron microscopy analysis of patient sperm Human mutation Medium 36135717
2020 Septin4 acts as a novel interacting protein of both STAT3 and SIRT1, forming a complex that enhances SIRT1-STAT3 interaction, promotes SIRT1-mediated deacetylation of STAT3-K685, and STAT3-Y705 dephosphorylation, thereby inhibiting PDGF-BB-induced HAVSMC proliferation, migration, and phenotypic transformation. Co-immunoprecipitation, knockdown and overexpression in HAVSMCs, phospho- and acetylation-specific immunoblotting International journal of biological sciences Medium 32025217
2020 Septin4 overexpression in VSMCs reduces autophagy and decreases Ang-II-induced proliferation and migration; inhibiting autophagy with chloroquine further restrains proliferation/migration in Septin4-overexpressing cells, indicating Septin4 modulates VSMC behavior through autophagy regulation. Overexpression in VSMCs, autophagy inhibition with chloroquine, proliferation and migration assays Biochemical and biophysical research communications Low 32085901
2014 Septin4_i1 (H5/PNUTL2 isoform) induces apoptosis in hepatic stellate cells (LX-2) through the PPAR-γ/Akt/Bcl-2 pathway: overexpression upregulates PPAR-γ and cleaved-caspase-3, and reduces phospho-Akt and Bcl-2; effects are reversed by a PPAR-γ antagonist or Akt activator. Overexpression in LX-2 cells, PPAR-γ antagonist and agonist treatment, Western blotting of pathway components The journal of histochemistry and cytochemistry Low 25527525
2014 Parkin-mediated ubiquitination of mutant glucocerebrosidase (GCase) competes with ubiquitination of its substrates ARTS and PARIS; accumulation of mutant GCase leads to increased ARTS levels and apoptosis in dopaminergic cells, linking mutant GCase, Parkin substrate competition, and ARTS-dependent apoptosis. Co-immunoprecipitation, competition ubiquitination assays, caspase activation assays in dopaminergic cells Orphanet journal of rare diseases Low 24935484

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Alteration of ionic selectivity of a K+ channel by mutation of the H5 region. Nature 360 1899917
2023 Alarming situation of emerging H5 and H7 avian influenza and effective control strategies. Emerging microbes & infections 198 36458831
2023 The episodic resurgence of highly pathogenic avian influenza H5 virus. Nature 197 37853121
2013 Receptor binding by a ferret-transmissible H5 avian influenza virus. Nature 197 23615615
2004 The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. The EMBO journal 151 15029247
1988 Alpha-helix in the carboxy-terminal domains of histones H1 and H5. The EMBO journal 150 3359996
2014 Selective protein denitrosylation activity of Thioredoxin-h5 modulates plant Immunity. Molecular cell 147 25201412
2006 Newcastle disease virus expressing H5 hemagglutinin gene protects chickens against Newcastle disease and avian influenza. Proceedings of the National Academy of Sciences of the United States of America 147 16717197
2023 The ARTS of p53-dependent mitochondrial apoptosis. Journal of molecular cell biology 119 36565718
1988 Footprinting of linker histones H5 and H1 on the nucleosome. The EMBO journal 113 3208745
2006 Protection against H1, H5, H6 and H9 influenza A infection with liposomal matrix 2 epitope vaccines. Vaccine 111 16713037
1998 A new human nm23 homologue (nm23-H5) specifically expressed in testis germinal cells. FEBS letters 98 9742940
2004 Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling. Current medicinal chemistry 96 15078170
2020 Genesis and spread of multiple reassortants during the 2016/2017 H5 avian influenza epidemic in Eurasia. Proceedings of the National Academy of Sciences of the United States of America 93 32769208
1998 Ion permeation and conduction in a human recombinant 5-HT3 receptor subunit (h5-HT3A). The Journal of physiology 93 9508827
2008 Establishment of retroviral pseudotypes with influenza hemagglutinins from H1, H3, and H5 subtypes for sensitive and specific detection of neutralizing antibodies. Journal of virological methods 87 18722473
2007 Detection of H5 avian influenza viruses by antigen-capture enzyme-linked immunosorbent assay using H5-specific monoclonal antibody. Clinical and vaccine immunology : CVI 85 17344345
2013 Sept4/ARTS regulates stem cell apoptosis and skin regeneration. Science (New York, N.Y.) 80 23788729
2020 Targeting XIAP for Promoting Cancer Cell Death-The Story of ARTS and SMAC. Cells 78 32182843
1994 Contacts of the globular domain of histone H5 and core histones with DNA in a "chromatosome". Proceedings of the National Academy of Sciences of the United States of America 78 8052665
2010 Sept4/ARTS is required for stem cell apoptosis and tumor suppression. Genes & development 76 20952537
2017 Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis. Cell reports 73 29020630
2013 "Shall I compare thee to a dose of donepezil?": cultural arts interventions in dementia care research. The Gerontologist 71 23749388
2006 Complex of linker histone H5 with the nucleosome and its implications for chromatin packing. Proceedings of the National Academy of Sciences of the United States of America 70 16717183
2017 Highly Pathogenic Influenza A(H5Nx) Viruses with Altered H5 Receptor-Binding Specificity. Emerging infectious diseases 67 27869615
2011 Safety and immunogenicity of influenza A H5 subunit vaccines: effect of vaccine schedule and antigenic variant. The Journal of infectious diseases 58 21282194
1983 The chicken H5 gene is unlinked to core and H1 histone genes. Nucleic acids research 56 6300759
2006 Risperidone irreversibly binds to and inactivates the h5-HT7 serotonin receptor. Molecular pharmacology 55 16870886
2005 ARTS: alignment of RNA tertiary structures. Bioinformatics (Oxford, England) 55 16204124
2022 Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development. Frontiers in immunology 53 35958612
2010 ARTS and Siah collaborate in a pathway for XIAP degradation. Molecular cell 51 21185211
2008 Development of vaccine strains of H5 and H7 influenza viruses. The Japanese journal of veterinary research 51 18318111
1990 Chromatin reconstitution on small DNA rings. III. Histone H5 dependence of DNA supercoiling in the nucleosome. Journal of molecular biology 50 2166168
2024 Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance. PLoS biology 49 39531474
1993 Histones H1 and H5 interact preferentially with crossovers of double-helical DNA. Proceedings of the National Academy of Sciences of the United States of America 48 8506351
2012 Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans. Clinical and vaccine immunology : CVI 46 22956656
1987 Structural analysis of a reconstituted DNA containing three histone octamers and histone H5. Journal of molecular biology 45 3441008
1992 Co-operative binding of the globular domain of histone H5 to DNA. Journal of molecular biology 44 1613793
2018 ARTS mediates apoptosis and regeneration of the intestinal stem cell niche. Nature communications 40 30389919
2023 Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy. Circulation research 38 36786216
2021 p53 induces ARTS to promote mitochondrial apoptosis. Cell death & disease 37 33627621
2009 Rapid detection of H5N1 subtype influenza viruses by antigen capture enzyme-linked immunosorbent assay using H5- and N1-specific monoclonal antibodies. Clinical and vaccine immunology : CVI 37 19321691
1990 Chromatin superstructure-dependent crosslinking with DNA of the histone H5 residues Thr1, His25 and His62. Journal of molecular biology 37 2106584
1989 Binding of the globular domain of linker histones H5/H1 to the nucleosome: a hypothesis. Protein engineering 37 2682606
2024 The mammary glands of cows abundantly display receptors for circulating avian H5 viruses. Journal of virology 35 39387556
1995 Assessment of a mutation in the H5 domain of Girk2 as a candidate for the weaver mutation. Genome research 35 8808466
1991 Inhibition of proliferation of primary avian fibroblasts through expression of histone H5 depends on the degree of phosphorylation of the protein. The Journal of cell biology 35 1849905
2015 Identification of Stabilizing Mutations in an H5 Hemagglutinin Influenza Virus Protein. Journal of virology 32 26719265
2012 Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein. PloS one 32 22792159
2005 Regulation of the proapoptotic ARTS protein by ubiquitin-mediated degradation. The Journal of biological chemistry 32 15837787
2017 Deubiquitinating enzymes Ubp2 and Ubp15 regulate endocytosis by limiting ubiquitination and degradation of ARTs. Molecular biology of the cell 31 28298493
2014 Expression of the Novel Costimulatory Molecule B7-H5 in Pancreatic Cancer. Annals of surgical oncology 30 25519928
2010 Complementary monoclonal antibody-based dot ELISA for universal detection of H5 avian influenza virus. BMC microbiology 29 21192824
2011 ARTS, the unusual septin: structural and functional aspects. Biological chemistry 28 21824006
2009 In vitro responses to avian influenza H5 by human CD4 T cells. Journal of immunology (Baltimore, Md. : 1950) 27 19841175
2014 Enhanced human receptor binding by H5 haemagglutinins. Virology 26 24889237
2014 Parkin-mediated ubiquitination of mutant glucocerebrosidase leads to competition with its substrates PARIS and ARTS. Orphanet journal of rare diseases 26 24935484
1988 Isolation and expression of cDNA clones coding for two sequence variants of Xenopus laevis histone H5. Gene 26 2907322
2015 Genetic Confirmation that the H5 Protein Is Required for Vaccinia Virus DNA Replication. Journal of virology 25 25855734
2020 A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2. Cell death & disease 24 32587235
2019 ARTs in Wild Felid Conservation Programmes in Poland and in the World. Journal of veterinary research 23 31572828
2018 Histone H5 is a potent Antimicrobial Agent and a template for novel Antimicrobial Peptides. Scientific reports 23 29402952
2016 Time-Motion and Biological Responses in Simulated Mixed Martial Arts Sparring Matches. Journal of strength and conditioning research 22 26817739
1985 DNA replication and H5 histone exchange during reactivation of chick erythrocyte nuclei in heterokaryons. Chromosoma 22 3996104
2016 Mosaic H5 Hemagglutinin Provides Broad Humoral and Cellular Immune Responses against Influenza Viruses. Journal of virology 21 27194759
2024 Immunogenicity and biodistribution of lipid nanoparticle formulated self-amplifying mRNA vaccines against H5 avian influenza. NPJ vaccines 20 39097672
2019 A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains. Vaccine 20 30905528
2011 Rapid PCR-based molecular pathotyping of H5 and H7 avian influenza viruses. Journal of clinical microbiology 20 21900520
2009 The effects of height and distance on the force production and acceleration in martial arts strikes. Journal of sports science & medicine 19 24474886
2004 Older adults and the arts: the importance of aesthetic forms of expression in later life. Journal of gerontological nursing 19 15471061
2024 Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects. Human reproduction update 18 37697674
2015 The arts, health, and aging in america: 2005-2015. The Gerontologist 18 26035603
2012 Serosurvey against H5 and H7 avian influenza viruses in Italian poultry workers. Avian diseases 18 23402138
2004 Influenza H5 virus escape mutants: immune protection and antibody production in mice. Virus research 18 14749187
2004 The ARTS connection: role of ARTS in apoptosis and cancer. Cell cycle (Georgetown, Tex.) 18 15254396
2020 Septin4 as an autophagy modulator regulates Angiotensin-II mediated VSMCs proliferation and migration. Biochemical and biophysical research communications 17 32085901
1985 Serological homologies between H1 degrees and H5 include the carboxyl-terminal domain. The Journal of biological chemistry 17 2415523
2022 Biallelic loss-of-function mutations in SEPTIN4 (C17ORF47), encoding a conserved annulus protein, cause thin midpiece spermatozoa and male infertility in humans. Human mutation 15 36135717
2013 Eudaimonic well-being and community arts participation. Perspectives in public health 15 23308009
2009 DNA vaccine encoding avian influenza virus H5 and Esat-6 of Mycobacterium tuberculosis improved antibody responses against AIV in chickens. Comparative immunology, microbiology and infectious diseases 15 19781778
2023 Structural insights into the assembly and mechanism of mpox virus DNA polymerase complex F8-A22-E4-H5. Molecular cell 14 37995690
2021 Plasticity of the Influenza Virus H5 HA Protein. mBio 14 33563825
2021 Broadly Reactive IgG Responses to Heterologous H5 Prime-Boost Influenza Vaccination Are Shaped by Antigenic Relatedness to Priming Strains. mBio 14 34225490
2018 Arts-Based Research Approaches to Studying Mechanisms of Change in the Creative Arts Therapies. Frontiers in psychology 14 30443230
2024 How the arts heal: a review of the neural mechanisms behind the therapeutic effects of creative arts on mental and physical health. Frontiers in behavioral neuroscience 13 39416439
2019 Structural and antigenic characterization of a computationally-optimized H5 hemagglutinin influenza vaccine. Vaccine 13 31481254
2015 Adenovirus-mediated over-expression of Septin4 ameliorates hepatic fibrosis in mouse livers infected with Schistosoma japonicum. Parasitology international 13 26190030
2008 Rapid discrimination of H5 and H9 subtypes of avian influenza viruses and Newcastle disease virus by multiplex RT-PCR. Veterinary research communications 13 18481190
1999 3-(Piperazinylpropyl)indoles: selective, orally bioavailable h5-HT1D receptor agonists as potential antimigraine agents. Journal of medicinal chemistry 13 10052976
1993 Transcription of the histone H5 gene is regulated by three differentiation-specific enhancers. Molecular and cellular biology 13 8336726
1982 Chicken histone H5: selection of a cDNA recombinant using an extended synthetic primer. Nucleic acids research 13 6896089
2020 Septin4 Prevents PDGF-BB-induced HAVSMC Phenotypic Transformation, Proliferation and Migration by Promoting SIRT1-STAT3 Deacetylation and Dephosphorylation. International journal of biological sciences 12 32025217
2014 Septin4_i1 regulates apoptosis in hepatic stellate cells through peroxisome proliferator-activated receptor-γ/Akt/B-cell lymphoma 2 pathway. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 12 25527525
2004 Receptor specificity of H5 influenza virus escape mutants. Virus research 12 15019242
2001 Localisation of mRNA for h5-HT1B and h5-HT1D receptors in human dorsal raphe. Naunyn-Schmiedeberg's archives of pharmacology 12 11284452
2001 Agonist properties of pindolol at h5-HT1A receptors coupled to mitogen-activated protein kinase. European journal of pharmacology 12 11470255
1991 Expression of arylhydrocarbon hydroxylase, epoxide hydrolases, glutathione S-transferase and UDP-glucuronosyltransferases in H5-6 hepatoma cells. General pharmacology 12 1936901
2018 EGFR may participate in immune evasion through regulation of B7‑H5 expression in non‑small cell lung carcinoma. Molecular medicine reports 11 30106102
2013 Expression of Septin4 in human hepatic stellate cells LX-2 stimulated by LPS. Inflammation 11 23180367
2023 Arts Therapy and Its Implications in Chronic Pain Management: A Narrative Review. Pain and therapy 10 37733173