Affinage

SEPTIN4

Septin-4 · UniProt O43236

Length
996 aa
Mass
112.4 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SEPTIN4 encodes two functionally divergent isoforms generated by alternative promoters, splicing, and intron retention: the mitochondrial pro-apoptotic isoform Sept4_i2/ARTS and the non-apoptotic Sept4_i1 (PMID:21824006). ARTS is a tumor-suppressive antagonist of the inhibitor-of-apoptosis protein XIAP: upon pro-apoptotic stimulation it is released from mitochondria and binds XIAP directly at the BIR1 domain, a site distinct from the caspase-binding pockets (PMID:15029247, PMID:21185211). Bound ARTS acts as an adaptor that bridges the E3 ligase Siah-1 to XIAP, driving XIAP ubiquitination and proteasomal degradation and thereby relieving caspase inhibition (PMID:21185211). ARTS additionally nucleates a ternary complex with XIAP and Bcl-2 in which XIAP ubiquitinates Bcl-2 at Lys17 to promote its degradation, and it binds and sequesters p53 at mitochondria to enhance the p53–Bcl-XL interaction; ARTS is itself a transcriptional target of p53 (PMID:29020630, PMID:33627621). This ARTS–XIAP axis governs apoptosis-dependent control of stem cell pools and tissue homeostasis: Sept4/ARTS loss elevates XIAP, protects hematopoietic, hair-follicle, and intestinal stem cells from death, accelerates tumorigenesis, and impairs inflammation resolution, with all phenotypes reverted by XIAP inactivation (PMID:20952537, PMID:23788729, PMID:30389919, PMID:32564202). In healthy cells ARTS is held at low levels by constitutive ubiquitin–proteasome turnover, mediated by Parkin and by WWP2-catalyzed ubiquitination at Lys174, with SIRT2-dependent deacetylation of the same residue modulating its pro-apoptotic activity in podocytes (PMID:15837787, PMID:22792159, PMID:31924572, PMID:36786216). Beyond apoptosis, Septin4 is an essential structural component of the sperm annulus required for midpiece integrity and SLC26A8 localization, and biallelic loss-of-function SEPTIN4 mutations cause asthenoteratozoospermia in humans (PMID:36135717). In the vasculature and myocardium Septin4 binds PARP1, SIRT1–STAT3, and the HIF-1α–VHL machinery to regulate endothelial injury, smooth muscle cell behavior, and cardiomyocyte apoptosis (PMID:29366480, PMID:32025217, PMID:34230460).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2004 High

    Established that the SEPTIN4 isoform ARTS is a mitochondrial pro-apoptotic protein that acts directly on XIAP, defining its core molecular target.

    Evidence In vitro binding with recombinant proteins, Co-IP, cell-based apoptosis assays, and mutagenesis in cell lines

    PMID:15029247

    Open questions at the time
    • Did not identify the binding domain on XIAP
    • Mechanism of how binding lowers XIAP levels left undefined
  2. 2005 Medium

    Showed why ARTS is dormant in living cells — it is held at low levels by constitutive ubiquitin-proteasome degradation that is relieved upon apoptotic signaling.

    Evidence Ubiquitination assays, proteasome inhibition, and protein stability experiments in cell lines

    PMID:15837787

    Open questions at the time
    • The responsible E3 ligase was not identified here
    • Signal that inhibits ARTS ubiquitination upon apoptotic induction unresolved
  3. 2010 High

    Resolved the molecular mechanism of XIAP destruction, showing ARTS binds the BIR1 domain and bridges the E3 ligase Siah-1 to drive XIAP ubiquitination.

    Evidence Reciprocal Co-IP, ubiquitination assays, and loss-of-function in ARTS- and Siah-deficient cells

    PMID:21185211

    Open questions at the time
    • Stoichiometry of the ARTS–Siah-1–XIAP complex not defined
    • No structural model of the BIR1 interface
  4. 2010 High

    Placed ARTS genetically upstream of XIAP in vivo, demonstrating it is a tumor suppressor that restrains hematopoietic stem cell survival.

    Evidence Sept4 knockout mice, Eµ-Myc tumor model, XIAP epistasis double knockout, FACS of stem/progenitor cells

    PMID:20952537

    Open questions at the time
    • Cell-type-specific contributions to tumor suppression not dissected
    • Does not address non-XIAP targets
  5. 2011 Medium

    Explained the divergent biology of the locus by characterizing two isoforms with distinct promoters, splicing, and subcellular localization.

    Evidence Promoter and splicing analysis plus subcellular fractionation/immunolocalization

    PMID:21824006

    Open questions at the time
    • Functional role of Sept4_i1 left largely undefined
    • Synthesis of prior data rather than new mechanism
  6. 2012 Medium

    Identified Parkin as an E3 ligase that selectively degrades ARTS, linking ARTS turnover to a neuronal survival pathway.

    Evidence Reciprocal Co-IP, ubiquitination assays, Parkin gain/loss-of-function, neuronal apoptosis assays, and a 6-OHDA rat model

    PMID:22792159

    Open questions at the time
    • Ubiquitination site on ARTS not mapped
    • Relationship between Parkin and other ARTS ligases unresolved
  7. 2013 High

    Extended the ARTS–XIAP axis to adult tissue regeneration, showing ARTS controls hair follicle stem cell apoptosis via XIAP.

    Evidence Sept4/ARTS knockout mice, lineage tracing, XIAP epistasis, wound healing assays

    PMID:23788729

    Open questions at the time
    • Upstream signals triggering ARTS in stem cells unknown
    • Whether effect is cell-autonomous within the niche not fully resolved
  8. 2017 High

    Expanded ARTS function beyond XIAP degradation, showing it nucleates an XIAP–Bcl-2 ternary complex enabling Bcl-2 ubiquitination at K17.

    Evidence Co-IP of the ternary complex, ubiquitylation assays, K17A/BH3 mutagenesis, knockout MEFs, mass spectrometry

    PMID:29020630

    Open questions at the time
    • Spatial/temporal coordination with XIAP degradation not resolved
    • Bcl-xL regulation mechanism less defined than Bcl-2
  9. 2018 High

    Demonstrated ARTS restrains intestinal stem cell survival and Wnt signaling, with phenotypes XIAP-dependent.

    Evidence Knockout mice, intestinal organoids, ARTS-XIAP Co-IP, XIAP epistasis, Wnt/β-catenin assays

    PMID:30389919

    Open questions at the time
    • Mechanistic link between ARTS loss and Wnt activation indirect
    • Direct ARTS effectors in crypt cells beyond XIAP unknown
  10. 2018 Medium

    Identified PARP1 as a novel Septin4 partner relevant to oxidative endothelial stress.

    Evidence Co-IP, Septin4 knockdown/overexpression, ROS and apoptosis assays in endothelial cells

    PMID:29366480

    Open questions at the time
    • Single Co-IP without reciprocal/structural validation
    • Functional consequence of the Septin4-PARP1 complex on PARP1 activity unclear
  11. 2020 High

    Defined WWP2 as a HECT E3 ligase that ubiquitinates Septin4 at K174 to suppress the Septin4-PARP1 endothelial damage complex.

    Evidence Co-IP, ubiquitination assays, K174 mutagenesis, endothelial-specific WWP2 knockout mice

    PMID:31924572

    Open questions at the time
    • Interplay between WWP2 and Parkin in Septin4 turnover not addressed
    • Isoform specificity of K174 ubiquitination not detailed
  12. 2020 Medium

    Showed Septin4 promotes formation of a SIRT1–STAT3 complex to suppress vascular smooth muscle cell proliferation through STAT3 deacetylation/dephosphorylation.

    Evidence Reciprocal Co-IP of ternary complex, gain/loss-of-function, STAT3 PTM analysis, VSMC functional assays

    PMID:32025217

    Open questions at the time
    • Direct vs scaffolding role of Septin4 in the complex unclear
    • Single-lab finding without structural mapping
  13. 2020 Medium

    Linked Septin4 to autophagy regulation in vascular smooth muscle cells controlling proliferation and migration.

    Evidence Septin4 overexpression, chloroquine epistasis, proliferation/migration assays, in vivo Ang-II infusion

    PMID:32085901

    Open questions at the time
    • No direct molecular link between Septin4 and the autophagy machinery
    • Mechanism of autophagy suppression undefined
  14. 2020 Medium

    Established a role for ARTS in resolution of inflammation through control of neutrophil apoptosis and macrophage efferocytosis.

    Evidence Sept4/ARTS knockout mice, zymosan peritonitis, leukocyte overexpression, efferocytosis and cytokine assays

    PMID:32564202

    Open questions at the time
    • Whether macrophage reprogramming is XIAP-dependent not directly tested
    • Cell-intrinsic vs extrinsic contributions not separated
  15. 2020 Medium

    Validated the ARTS-binding pocket on XIAP pharmacologically, showing a small molecule recapitulates ARTS-driven XIAP/Bcl-2 degradation and apoptosis.

    Evidence Microscale thermophoresis, ubiquitylation and caspase assays, XIAP rescue, cancer cell proteome analysis

    PMID:32587235

    Open questions at the time
    • Compound binds BIR3, leaving exact correspondence to ARTS BIR1 site partly inferential
    • Selectivity in vivo not established
  16. 2021 High

    Connected ARTS to the p53 axis as both a transcriptional target and a mitochondrial p53-sequestering factor that promotes apoptosis.

    Evidence Luciferase reporter, ChIP, reciprocal Co-IP, gain/loss-of-function, in vivo irradiation

    PMID:33627621

    Open questions at the time
    • Stoichiometry and structural basis of ARTS-p53 binding unknown
    • Interplay with the XIAP-degradation function not integrated
  17. 2021 Medium

    Showed Septin4 enhances HIF-1α–VHL binding to drive HIF-1α degradation, aggravating cardiomyocyte apoptosis under hypoxia.

    Evidence Co-IP, GTPase domain mapping, ubiquitination assays, cardiomyocyte hypoxia model

    PMID:34230460

    Open questions at the time
    • Direct contact residues between Septin4 and HIF-1α undefined
    • Single-lab finding without in vivo validation
  18. 2022 High

    Defined a structural, apoptosis-independent role for SEPTIN4, establishing it as essential for the sperm annulus and a cause of human asthenoteratozoospermia.

    Evidence Human biallelic loss-of-function variants, immunofluorescence, immunoblotting, electron microscopy of sperm

    PMID:36135717

    Open questions at the time
    • Mechanism of SLC26A8 mislocalization not detailed
    • How structural and apoptotic functions are partitioned between isoforms unclear
  19. 2023 High

    Identified an acetylation switch on Septin4-K174 controlled by SIRT2 that tunes its pro-apoptotic activity in hypertensive renal injury.

    Evidence Transgenic/knockout SIRT2 mice, K174Q/R knock-in mice, Co-IP, mass spectrometry, acetyl-proteomics

    PMID:36786216

    Open questions at the time
    • Crosstalk between K174 acetylation and K174 ubiquitination by WWP2 not directly resolved
    • Generalizability beyond podocytes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the apoptotic ARTS isoform and the structural/scaffolding Septin4 functions are coordinated at the protein level, and whether the cytoplasmic vascular/cardiac partner interactions (PARP1, SIRT1-STAT3, HIF-1α-VHL) involve canonical septin filament assembly, remains unresolved.
  • No structural model of ARTS-XIAP or ARTS-p53 complexes
  • Isoform-specific contributions to vascular and cardiac phenotypes not dissected
  • Relationship between septin polymerization and the apoptotic adaptor function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 1
Localization
GO:0005739 mitochondrion 4 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-5357801 Programmed Cell Death 6 R-HSA-1474165 Reproduction 1 R-HSA-1643685 Disease 1
Partners
BCL2PARK2PARP1SIAH1SIRT2TP53WWP2XIAP
Complex memberships
ARTS-XIAP-Bcl-2 ternary complexARTS-XIAP-Siah-1 complexSeptin4-SIRT1-STAT3 complexsperm annulus

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 ARTS (Sept4_i2) is released from mitochondria upon pro-apoptotic stimuli and directly binds XIAP in vitro; binding is specific and required for pro-apoptotic function, as ARTS mutants that fail to bind XIAP also fail to induce apoptosis. ARTS binding to XIAP leads to decreased XIAP protein levels and caspase activation. In vitro binding assay with recombinant proteins, coimmunoprecipitation, cell-based apoptosis assays, mutagenesis of ARTS and related septins The EMBO journal High 15029247
2010 ARTS binds XIAP at the BIR1 domain (distinct from caspase-binding sites) and interacts with the E3 ligase Siah-1, acting as an adaptor to bridge Siah-1 to XIAP, thereby inducing XIAP ubiquitination and degradation. Cells lacking either Siah or ARTS have elevated steady-state XIAP levels. Co-immunoprecipitation, ubiquitination assays, genetic knockdown/knockout of ARTS and Siah in cells Molecular cell High 21185211
2017 ARTS forms a ternary complex with XIAP and Bcl-2 at the outer mitochondrial membrane upon apoptotic induction. ARTS binding to Bcl-2 involves the BH3 domain of Bcl-2; XIAP serves as an E3 ligase ubiquitinating Bcl-2 at Lysine 17, and ARTS is essential for this process. A Bcl-2 K17A mutant has increased stability and stronger anti-apoptotic potency. Bcl-2 ubiquitylation is reduced in both XIAP- and Sept4/ARTS-deficient MEFs. Co-immunoprecipitation (ternary complex), ubiquitylation assays, site-directed mutagenesis (K17A Bcl-2, BH3 domain), MEF knockout cells, mass spectrometry Cell reports High 29020630
2005 ARTS protein levels are kept low in healthy cells through constant ubiquitin-mediated proteasomal degradation. Upon pro-apoptotic stimuli, ARTS ubiquitination is inhibited, leading to increased ARTS levels, decreased Bcl-2 and Bcl-xL protein levels, cytochrome c release, and apoptosis. Ubiquitination assays, proteasome inhibitor treatments, overexpression and protein stability experiments in cell lines The Journal of biological chemistry Medium 15837787
2012 Parkin (E3-ubiquitin ligase) binds both ARTS (Sept4_i2) and Sept4_i1 but specifically ubiquitinates and degrades only ARTS via the ubiquitin-proteasome system. Parkin loss-of-function increases ARTS levels and promotes apoptosis; Parkin overexpression protects cells from ARTS-induced apoptosis. High ARTS levels are found in rat brains treated with 6-OHDA. Co-immunoprecipitation, ubiquitination assays, Parkin overexpression and knockdown, neuronal cell culture apoptosis assays, in vivo 6-OHDA rat model PloS one Medium 22792159
2010 Deletion of the mouse Sept4 gene (encoding ARTS) results in increased numbers of hematopoietic stem and progenitor cells, elevated XIAP protein, increased resistance to cell death, and accelerated tumor development in an Eμ-Myc background. These phenotypes are partially suppressed by inactivation of XIAP, placing ARTS upstream of XIAP in the apoptotic pathway. Sept4 knockout mice, Eμ-Myc tumor model, XIAP genetic inactivation (epistasis), FACS of hematopoietic stem/progenitor cells 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. Inactivation of XIAP, a direct ARTS target, abrogates these phenotypes, demonstrating ARTS acts via XIAP to regulate stem cell apoptosis and tissue regeneration. Sept4/ARTS knockout mice, lineage tracing, XIAP genetic inactivation, wound healing assays Science High 23788729
2018 ARTS is highly expressed in intestinal stem cell niche cells; its deletion protects Lgr5+ and Paneth cells from apoptosis, leading to augmented crypt proliferation, enhanced Wnt/β-catenin signaling, and massive cystic organoids. ARTS interacts with XIAP in intestinal crypt cells and deletion of XIAP abrogates Sept4/ARTS-/- phenotypes. Sept4/ARTS knockout mice, intestinal organoid culture, co-immunoprecipitation (ARTS-XIAP), XIAP genetic epistasis, Wnt/β-catenin signaling assays Nature communications High 30389919
2021 ARTS is a p53 target gene: p53 transcriptionally activates the ARTS promoter via a p53-responsive DNA element. In turn, ARTS binds p53 protein and sequesters it at mitochondria, enhancing interaction between p53 and Bcl-XL, thereby promoting mitochondrial apoptosis. Ectopic ARTS augments DNA damage-induced apoptosis; ablation of ARTS impairs p53-induced apoptosis. Luciferase reporter assay (ARTS promoter), ChIP (p53 binding to ARTS promoter), co-immunoprecipitation (ARTS-p53, p53-Bcl-XL), ARTS knockdown/overexpression, γ-irradiation in mice Cell death & disease High 33627621
2011 The Sept4 gene encodes two major isoforms (Sept4_i1/H5/PNUTL2 and Sept4_i2/ARTS) through a combination of two distinct promoters, differential splicing, and intron retention. ARTS is localized at mitochondria and promotes apoptosis, while Sept4_i1 is non-apoptotic; these structural differences explain their divergent biological activities. Molecular characterization (promoter analysis, splicing analysis), subcellular fractionation/immunolocalization Biological chemistry Medium 21824006
2020 WWP2 (a HECT-type E3 ubiquitin ligase) interacts with the GTPase domain of Septin4 and ubiquitinates Septin4 at K174, promoting its degradation via the ubiquitin-proteasome system. This inhibits the Septin4-PARP1 endothelial damage complex. Endothelial/myeloid-specific WWP2 knockout in mice aggravates oxidative stress-induced endothelial injury. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K174), WWP2 knockout mice (endothelial-specific), in vitro endothelial injury assays Redox biology High 31924572
2018 Septin4 directly interacts with PARP1 (identified as a novel binding partner), and this interaction is enhanced under oxidative stress. Knockdown and overexpression of Septin4 modulate ROS production and apoptosis in endothelial cells under oxidative stress. Co-immunoprecipitation (Septin4-PARP1), Septin4 knockdown and overexpression, ROS assays, apoptosis assays Biochemical and biophysical research communications Medium 29366480
2023 SIRT2 deacetylates Septin4 at lysine 174 (K174); hyperacetylation of K174 (mimicked by K174Q mutant) activates the cleaved-PARP1-cleaved-caspase3 pathway and exacerbates angiotensin II-induced hypertensive renal injury. Septin4-K174R (deacetylation mimic) rescues podocyte apoptosis. SIRT2 interacts with the Septin4 GTPase domain. Transgenic SIRT2 mice, SIRT2 knockout mice, septin4-K174Q and K174R mutant knock-in mice, co-immunoprecipitation, mass spectrometry, proteomic/acetyl-proteomics, Western blot Circulation research High 36786216
2020 Septin4 modulates autophagy in vascular smooth muscle cells (VSMCs); overexpression of Septin4 reduces autophagy levels and decreases Ang-II-induced VSMC proliferation and migration. Blocking autophagy with chloroquine further restrains proliferation and migration in Septin4-overexpressing VSMCs, confirming Septin4 regulates these processes via autophagy. Septin4 overexpression in VSMCs, autophagy inhibition with chloroquine, proliferation and migration assays, in vivo Ang-II infusion in mice Biochemical and biophysical research communications Medium 32085901
2020 Septin4 forms a complex with SIRT1 and STAT3 (co-immunoprecipitation), enhancing the interaction between SIRT1 and STAT3 and promoting SIRT1-regulated STAT3-K685 deacetylation and STAT3-Y705 dephosphorylation, thereby inhibiting PDGF-BB-induced HAVSMC proliferation, migration, and phenotypic transformation. Co-immunoprecipitation (Septin4-SIRT1-STAT3 complex), Septin4 knockdown and overexpression, phosphorylation and acetylation site analysis, VSMC functional assays International journal of biological sciences Medium 32025217
2021 Septin4 interacts with HIF-1α at the Septin4 GTPase domain and enhances the binding between HIF-1α and the E3 ubiquitin ligase VHL, promoting HIF-1α ubiquitin-mediated degradation. By reducing HIF-1α levels, Septin4 aggravates hypoxia-induced cardiomyocyte apoptosis. Co-immunoprecipitation (Septin4-HIF-1α, HIF-1α-VHL), GTPase domain mapping, ubiquitination assays, cardiomyocyte hypoxia model Cell death discovery Medium 34230460
2022 Biallelic loss-of-function mutations in SEPTIN4 (c.A721T/p.R241* and c.C205T/p.R69*) in humans cause thin midpiece spermatozoa, annulus loss, disorganized mitochondrial sheath, and asthenoteratozoospermia. SEPT4 is required for SEPT-based annulus formation and correct localization of SEPTIN subunits and the anion transporter SLC26A8 at the sperm annulus. Human genetics (biallelic variant identification), immunofluorescence, immunoblotting (TOMM20, HSP60, SLC26A8), electron microscopy of sperm ultrastructure Human mutation High 36135717
2020 In Sept4/ARTS-/- mice, neutrophil apoptosis, macrophage efferocytosis, and macrophage reprogramming to pro-resolving phenotype are all impaired during resolution of inflammation (zymosan-induced peritonitis). ARTS overexpression in leukocytes in vitro promotes anti-inflammatory behavior, indicating ARTS acts upstream of XIAP to regulate apoptosis-dependent resolution of inflammation. Sept4/ARTS-/- mice, zymosan-induced peritonitis model, ARTS overexpression in leukocytes, cytokine measurements, efferocytosis assays Apoptosis Medium 32564202
2014 Septin4_i1 induces apoptosis in hepatic stellate cells (LX-2) by upregulating PPAR-γ and reducing phosphorylated Akt and Bcl-2 expression. Cleaved-caspase-3 increases upon Septin4_i1 overexpression, and this effect is reversed by a PPAR-β/δ agonist (GW501516, which enhances Akt signaling) or a PPAR-γ antagonist (GW9662). Overexpression of Septin4_i1 in LX-2 cells, pharmacological inhibitor/agonist treatment, Western blot for PPAR-γ, Akt, Bcl-2, caspase-3 The journal of histochemistry and cytochemistry Medium 25527525
2020 A small molecule (A4) mimicking ARTS binds XIAP at a distinct pocket in the BIR3 domain (not the caspase-binding site, consistent with ARTS binding at BIR1 region), stimulates poly-ubiquitylation and UPS-mediated degradation of XIAP and Bcl-2 (but not cIAP1), activates caspase-9 and -3, and induces apoptosis. XIAP overexpression rescues cells from A4-induced death. Microscale thermophoresis (binding assay), ubiquitylation assays, caspase activation assays, XIAP overexpression rescue, proteome analysis of cancer cell lines Cell death & disease Medium 32587235

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. The Journal of clinical investigation 177 12189246
2004 The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. The EMBO journal 151 15029247
2005 MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes. The Journal of biological chemistry 147 15695812
2023 The ARTS of p53-dependent mitochondrial apoptosis. Journal of molecular cell biology 128 36565718
2002 Antigenicity and immunogenicity of Melan-A/MART-1 derived peptides as targets for tumor reactive CTL in human melanoma. Immunological reviews 122 12445283
2004 Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling. Current medicinal chemistry 96 15078170
2008 Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic melanoma. Journal of immunotherapy (Hagerstown, Md. : 1997) 90 18317358
1995 Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Cancer research 86 7531614
2013 Sept4/ARTS regulates stem cell apoptosis and skin regeneration. Science (New York, N.Y.) 80 23788729
2009 MART-1-specific melanoma tumor-infiltrating lymphocytes maintaining CD28 expression have improved survival and expansion capability following antigenic restimulation in vitro. Journal of immunology (Baltimore, Md. : 1950) 80 19949105
2020 Targeting XIAP for Promoting Cancer Cell Death-The Story of ARTS and SMAC. Cells 79 32182843
2010 Sept4/ARTS is required for stem cell apoptosis and tumor suppression. Genes & development 76 20952537
1998 High expression of immunotherapy candidate proteins gp100, MART-1, tyrosinase and TRP-1 in uveal melanoma. British journal of cancer 76 9820172
2017 Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis. Cell reports 74 29020630
2013 "Shall I compare thee to a dose of donepezil?": cultural arts interventions in dementia care research. The Gerontologist 72 23749388
2004 HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. Human pathology 70 14991540
1997 Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy. International reviews of immunology 67 9131386
2022 Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development. Frontiers in immunology 61 35958612
2005 ARTS: alignment of RNA tertiary structures. Bioinformatics (Oxford, England) 55 16204124
2020 Role of WW domain E3 ubiquitin protein ligase 2 in modulating ubiquitination and Degradation of Septin4 in oxidative stress endothelial injury. Redox biology 53 31924572
2010 ARTS and Siah collaborate in a pathway for XIAP degradation. Molecular cell 51 21185211
1996 Expression of MAGE-1, MAGE-3 and MART-1 genes in neuroblastoma. International journal of cancer 48 8900375
1997 Differential expression of MART-1 in primary and metastatic melanoma lesions. Journal of immunotherapy (Hagerstown, Md. : 1997) 45 9409451
2016 Neuroprotective Effects of Açaí (Euterpe oleracea Mart.) against Rotenone In Vitro Exposure. Oxidative medicine and cellular longevity 42 27781077
2023 Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy. Circulation research 41 36786216
2018 ARTS mediates apoptosis and regeneration of the intestinal stem cell niche. Nature communications 40 30389919
2006 Cardiotonic and sedative effects of Cecropia pachystachya Mart. (ambay) on isolated rat hearts and conscious mice. Journal of ethnopharmacology 40 16413716
2021 p53 induces ARTS to promote mitochondrial apoptosis. Cell death & disease 38 33627621
2014 Misinitiation of intrathymic MART-1 transcription and biased TCR usage explain the high frequency of MART-1-specific T cells. European journal of immunology 38 24846220
2014 Cytotoxic effects of Euterpe oleracea Mart. in malignant cell lines. BMC complementary and alternative medicine 38 24886139
2013 Açai (Euterpe oleracea Mart.) feeding attenuates dimethylhydrazine-induced rat colon carcinogenesis. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 37 23597449
2004 Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion. Blood 37 15073035
2004 HMB-45 (gp103) and MART-1 expression within giant cells in an atypical fibroxanthoma: a case report. Journal of cutaneous pathology 34 14984584
2020 Açaí (Euterpe oleracea Mart.) and juçara (Euterpe edulis Mart.) juices improved HDL-c levels and antioxidant defense of healthy adults in a 4-week randomized cross-over study. Clinical nutrition (Edinburgh, Scotland) 33 32349893
2019 Cochlospermum regium (Mart. ex Schrank) Pilg.: Evaluation of chemical profile, gastroprotective activity and mechanism of action of hydroethanolic extract of its xylopodium in acute and chronic experimental models. Journal of ethnopharmacology 33 30611907
2012 Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein. PloS one 33 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
2019 Antidepressant and Antiaging Effects of Açaí (Euterpe oleracea Mart.) in Mice. Oxidative medicine and cellular longevity 30 31428223
2011 ARTS, the unusual septin: structural and functional aspects. Biological chemistry 29 21824006
2007 MarT activates expression of the MisL autotransporter protein of Salmonella enterica serotype Typhimurium. Journal of bacteriology 29 17351045
2021 Phytochemical screening, phenolic and flavonoid contents, antioxidant and cytogenotoxicity activities of Combretum leprosum Mart. (Combretaceae). Journal of toxicology and environmental health. Part A 28 33494643
2005 Differential expression of MART-1, tyrosinase, and SM5-1 in primary and metastatic melanoma. The American Journal of dermatopathology 28 16148409
2020 Antioxidant, antiproliferative and healing properties of araticum (Annona crassiflora Mart.) peel and seed. Food research international (Ottawa, Ont.) 27 32466931
2010 Molecular mechanism of MART-1+/A*0201+ human melanoma resistance to specific CTL-killing despite functional tumor-CTL interaction. Cancer research 26 21159666
2021 Using mobile brain/body imaging to advance research in arts, health, and related therapeutics. The European journal of neuroscience 25 33999462
2011 S-MART, a software toolbox to aid RNA-Seq data analysis. PloS one 25 21998740
2020 A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2. Cell death & disease 24 32587235
2024 Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects. Human reproduction update 22 37697674
2022 ARTS-DB: a database for antibiotic resistant targets. Nucleic acids research 22 34718689
2016 Time-Motion and Biological Responses in Simulated Mixed Martial Arts Sparring Matches. Journal of strength and conditioning research 22 26817739
2019 Euterpe oleracea Mart. (Açai) Supplementation Attenuates Acute Doxorubicin-Induced Cardiotoxicity in Rats. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 31403269
2017 Cytotoxic analysis and chemical characterization of fractions of the hydroalcoholic extract of the Euterpe oleracea Mart. seed in the MCF-7 cell line. The Journal of pharmacy and pharmacology 21 28211563
2016 The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential. International journal of molecular sciences 21 27110769
1997 Cloning and analysis of MART-1/Melan-A human melanoma antigen promoter regions. Gene 21 9218710
2020 The pro-apoptotic ARTS protein induces neutrophil apoptosis, efferocytosis, and macrophage reprogramming to promote resolution of inflammation. Apoptosis : an international journal on programmed cell death 20 32564202
2015 Antibacterial, antibiofilm and cytotoxic activities of Terminalia fagifolia Mart. extract and fractions. Annals of clinical microbiology and antimicrobials 20 25902872
2011 A mart-1::Cre transgenic line induces recombination in melanocytes and retinal pigment epithelium. Genesis (New York, N.Y. : 2000) 20 21309074
2005 Cotransfection of DC with TLR4 and MART-1 RNA induces MART-1-specific responses. The Journal of surgical research 20 15820257
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 19 39416439
2021 Açaí (Euterpe oleracea Mart.) as a Potential Anti-neuroinflammatory Agent: NLRP3 Priming and Activating Signal Pathway Modulation. Molecular neurobiology 19 34021869
2019 Creative Arts Therapy in the Context of Children With Cancer: A Concept Analysis. Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses 19 31592707
2016 Guarana (Paullinia cupana Mart.) attenuates methylmercury-induced toxicity in Caenorhabditis elegans. Toxicology research 19 28316775
2011 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro. The Journal of investigative dermatology 19 21993558
1997 Martial arts injuries. The Journal of the American Osteopathic Association 19 9154740
2015 The arts, health, and aging in america: 2005-2015. The Gerontologist 18 26035603
2004 The ARTS connection: role of ARTS in apoptosis and cancer. Cell cycle (Georgetown, Tex.) 18 15254396
2002 Expression of tyrosinase, MIA and MART-1 in sentinel lymph nodes of patients with malignant melanoma. The British journal of dermatology 18 11903234
2020 Septin4 as an autophagy modulator regulates Angiotensin-II mediated VSMCs proliferation and migration. Biochemical and biophysical research communications 17 32085901
2018 Septin4 as a novel binding partner of PARP1 contributes to oxidative stress induced human umbilical vein endothelial cells injure. Biochemical and biophysical research communications 17 29366480
2015 Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats. Drug and chemical toxicology 17 25791997
2020 Açaí (Euterpe oleracea Mart.) presents anti-neuroinflammatory capacity in LPS-activated microglia cells. Nutritional neuroscience 16 33170113
2022 Phytochemical Analysis of the Fruit Pulp Extracts from Annona crassiflora Mart. and Evaluation of Their Antioxidant and Antiproliferative Activities. Foods (Basel, Switzerland) 15 35885322
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
2022 Anti-Candida albicans Activity of Ononin and Other Secondary Metabolites from Platonia Insignis MART. Metabolites 14 36355097
2020 Açaí (Euterpe oleracea Mart.) seed extract improves aerobic exercise performance in rats. Food research international (Ottawa, Ont.) 14 32846601
2018 Arts-Based Research Approaches to Studying Mechanisms of Change in the Creative Arts Therapies. Frontiers in psychology 14 30443230
2020 Euterpe oleracea Mart. (Açaí) attenuates experimental colitis in rats: involvement of TLR4/COX-2/NF-ĸB. Inflammopharmacology 13 32996043
2019 Chemical composition and antiproliferative, antioxidant and trypanocidal activities of the fruits from Campomanesia xanthocarpa (Mart.) O. Berg (Myrtaceae). Natural product research 13 31090448
2015 Adenovirus-mediated over-expression of Septin4 ameliorates hepatic fibrosis in mouse livers infected with Schistosoma japonicum. Parasitology international 13 26190030
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 13 25527525
2007 The pro-apoptotic ARTS/Sept4 protein is significantly reduced in post-mortem brains from schizophrenic patients. Schizophrenia research 13 17644312
2021 Free to be: Experiences of arts-based relational caring in a community living and thriving with dementia. Dementia (London, England) 12 34166151
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
2015 Expression of Septin4 in Schistosoma japonicum-infected mouse livers after praziquantel treatment. Parasites & vectors 12 25582427
2014 Deciphering the unusual HLA-A2/Melan-A/MART-1-specific TCR repertoire in humans. European journal of immunology 12 25154881
2008 Antioxidant and hepatoprotective effects of Cyathea phalerata Mart. (Cyatheaceae). Basic & clinical pharmacology & toxicology 12 18482221
1997 The arts in spiritual care. Seminars in oncology nursing 12 9392030
2023 Arts Therapy and Its Implications in Chronic Pain Management: A Narrative Review. Pain and therapy 11 37733173
2020 Regulation of biofilm formation by marT in Salmonella Typhimurium. Molecular biology reports 11 32529277
2019 How Does Creative Arts Therapy Reduce Distress for Children With Cancer? A Metasynthesis of Extant Qualitative Literature. Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses 11 31766942
2018 Hexane partition from Annona crassiflora Mart. promotes cytotoxity and apoptosis on human cervical cancer cell lines. Investigational new drugs 11 30155717
2013 Expression of Septin4 in human hepatic stellate cells LX-2 stimulated by LPS. Inflammation 11 23180367
2011 Antiproliferative activity of three methoxylated flavonoids isolated from Zeyheria montana Mart. (Bignoniaceae) leaves. Phytotherapy research : PTR 11 21351299
2021 Plastid genome evolution in Amazonian açaí palm (Euterpe oleracea Mart.) and Atlantic forest açaí palm (Euterpe edulis Mart.). Plant molecular biology 10 33386578
2021 Septin4 promotes cardiomyocytes apoptosis by enhancing the VHL-mediated degradation of HIF-1α. Cell death discovery 10 34230460
2018 Arts-based psychiatric rehabilitation programs in the community: Perceptions of healthcare professionals. Psychiatric rehabilitation journal 10 30221966
2010 Lovastatin inhibits T-cell proliferation while preserving the cytolytic function of EBV, CMV, and MART-1-specific CTLs. Journal of immunotherapy (Hagerstown, Md. : 1997) 10 20948439
2007 Time for Me: the arts as therapy in postnatal depression. Complementary therapies in clinical practice 10 18243941

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