Affinage

ACTL6A

Actin-like protein 6A · UniProt O96019

Length
429 aa
Mass
47.5 kDa
Annotated
2026-04-28
52 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACTL6A (BAF53a/Arp4) is an actin-related protein that functions as a stoichiometric subunit of multiple chromatin remodeling and histone-modifying complexes—including SWI/SNF (BAF), INO80, NuA4/TIP60, and SWR1—where it controls chromatin accessibility, transcription factor binding, and gene expression across diverse cellular contexts. ACTL6A forms an obligate heterocomplex with β-actin that is required for incorporation into and stabilization of SWI/SNF complexes; disruption of this interaction accelerates BRG1 degradation and impairs complex integrity (PMID:22573825). Within the INO80 complex, ACTL6A binds extranucleosomal DNA and functions as a DNA-length sensor that couples ATP hydrolysis to nucleosome sliding (PMID:30120252), while within NuA4/TIP60 it directly binds the catalytic acetyltransferase subunit and is required for histone H4 and H3K9 acetylation (PMID:15483052, PMID:17395615, PMID:32112486). A key biological function of ACTL6A is maintaining the progenitor/undifferentiated state in epithelia, hematopoietic stem cells, ESCs, and Schwann cells by preventing SWI/SNF-mediated activation of differentiation gene promoters—including those driven by KLF4, NRF2, BACH1, and AP-1—and its dosage within BAF complexes determines whether polycomb is opposed at regulatory regions, enabling co-loading of TEAD-YAP and other oncogenic transcription factors in squamous cell carcinoma (PMID:23395444, PMID:23018638, PMID:34687603, PMID:37443154, PMID:40877226).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing that the ACTL6A ortholog (Arp4) directly binds histones via a unique insertion domain and affects chromatin structure resolved how an actin-related protein interfaces with nucleosomes.

    Evidence Far Western, two-hybrid, and co-IP with histones in budding yeast

    PMID:10436015

    Open questions at the time
    • Whether mammalian ACTL6A retains this histone-binding mode
    • Structural resolution of the insertion II domain–histone interface
  2. 2002 High

    Demonstrating that Arp4 occupies specific promoters in vivo and its loss alters chromatin and transcription established ACTL6A as a direct transcriptional regulator via chromatin remodeling.

    Evidence ChIP and conditional mutation with nuclease sensitivity assays at yeast his4-912δ promoter

    PMID:11937627

    Open questions at the time
    • Identity of target genes in mammalian cells
    • Whether Arp4 acts through SWI/SNF, INO80, or NuA4 at this locus
  3. 2004 High

    Linking the ACTL6A ortholog Alp5 to HAT-dependent histone H4 acetylation and centromeric silencing established its role in histone modification and chromosome segregation fidelity.

    Evidence Acetyl-histone immunoblotting, genetic epistasis with HDAC inhibitors, and spindle checkpoint analysis in fission yeast

    PMID:15483052

    Open questions at the time
    • Whether mammalian ACTL6A similarly regulates centromeric acetylation
    • Mechanism by which Alp5 stimulates HAT activity
  4. 2007 High

    Showing that Arp4 occupies centromeric and telomeric chromatin throughout the cell cycle and is required for kinetochore assembly placed ACTL6A within INO80, NuA4, and SWR1 complexes at specialized chromosome domains.

    Evidence ChIP across the cell cycle, conditional mutant analysis of kinetochore components in budding yeast

    PMID:17395615 PMID:17452364

    Open questions at the time
    • Relative contribution of each complex (INO80, NuA4, SWR1) to kinetochore function
    • Whether mammalian ACTL6A has analogous centromeric roles
  5. 2012 High

    Two studies resolved essential mammalian functions: ACTL6A forms a β-actin heterocomplex required for SWI/SNF and TIP60 complex integrity, and its conditional deletion causes lethal bone marrow failure, establishing cell-autonomous requirements in human complex assembly and adult tissue homeostasis.

    Evidence Co-IP, mutagenesis, and RNAi in human cells; conditional KO mouse with hematopoietic chimera transplantation

    PMID:22573825 PMID:23018638

    Open questions at the time
    • Structure of the ACTL6A–β-actin heterocomplex within BAF
    • Molecular basis of lineage-specific progenitor dependence on ACTL6A
  6. 2013 High

    Conditional KO in epidermis revealed that ACTL6A prevents SWI/SNF from binding differentiation gene promoters (including KLF4), establishing the paradigm that ACTL6A actively restrains chromatin remodeler access to maintain the progenitor state.

    Evidence Conditional KO mouse epidermis, ChIP showing SWI/SNF recruitment upon ACTL6A loss, gene expression profiling

    PMID:23395444

    Open questions at the time
    • Whether ACTL6A sterically blocks SWI/SNF binding or alters complex conformation
    • Mechanism of subunit-level selectivity for differentiation gene promoters
  7. 2015 High

    Identifying ACTL6A interactions with Nanog and Sox2, and showing that a TIP60/p400-binding mutant fails to block primitive endoderm differentiation, connected ACTL6A to pluripotency transcription factor networks through specific complex engagement.

    Evidence Co-IP, ChIP, RNAi, and mutant rescue in mouse ESCs

    PMID:25802002

    Open questions at the time
    • Whether ACTL6A–Nanog interaction is direct or bridged through BAF/TIP60
    • How TIP60/p400 versus BAF complex contributions are partitioned in ESC fate
  8. 2018 High

    Biochemical reconstitution of the INO80 complex revealed that ACTL6A (with Arp8) senses extranucleosomal DNA length, coupling this measurement to nucleosome sliding—providing the first defined catalytic contribution of ACTL6A to remodeling.

    Evidence In vitro DNA binding, mutagenesis, and nucleosome sliding assays with reconstituted INO80

    PMID:30120252

    Open questions at the time
    • Whether this DNA-length sensing applies to mammalian INO80 in vivo
    • How ACTL6A communicates with the Arp5-acidic patch contact mechanistically
  9. 2020 High

    Multiple advances converged: ACTL6A was shown to suppress nuclear F-actin polymerization, directly bind and repress the p21 promoter independent of p53, and regulate histone H3K9 acetylation for pluripotency—broadening its functional repertoire beyond chromatin remodeling complex subunit roles.

    Evidence Purified Arp4 inhibition of F-actin in Xenopus oocyte nuclear transplant; ChIP and reporter assays at p21 promoter in SCC; H3K9ac analysis in iPSCs

    PMID:32112486 PMID:32204557 PMID:32616890

    Open questions at the time
    • Structural basis of F-actin suppression by ACTL6A
    • Whether p21 repression requires SWI/SNF or is a direct DNA-binding function
    • Whether H3K9ac regulation is through TIP60 or an alternative acetyltransferase
  10. 2021 High

    Showing that ACTL6A overexpression drives stoichiometric BAF assembly that opposes polycomb genome-wide and enables co-loading of BAF with TEAD-YAP at SCC regulatory regions explained how ACTL6A dosage—normally substoichiometric—becomes oncogenic.

    Evidence ATAC-seq, ChIP-seq, quantitative proteomics of BAF composition in SCC versus normal cells

    PMID:34687603

    Open questions at the time
    • What controls ACTL6A stoichiometry in normal cells
    • Whether therapeutic reduction of ACTL6A dosage reverses SCC chromatin state
  11. 2021 High

    ACTL6A overexpression enhanced repair of cisplatin-DNA adducts through SWI/SNF, and HDAC inhibition reversed this repair, connecting ACTL6A to DNA damage repair and chemoresistance.

    Evidence DNA adduct repair assay, gain/loss-of-function, HDAC inhibitor treatment in xenografts

    PMID:33408251

    Open questions at the time
    • Which SWI/SNF subcomplex (BAF vs. PBAF) mediates repair
    • Direct versus indirect role of ACTL6A in damage recognition
  12. 2022 Medium

    Discovery that FBXW7 ubiquitinates and degrades ACTL6A identified the first E3 ligase controlling ACTL6A protein turnover, providing a mechanism for dosage regulation.

    Evidence Co-IP, in vivo ubiquitination assay in HCC cells

    PMID:36159747

    Open questions at the time
    • Degron motif in ACTL6A recognized by FBXW7
    • Whether FBXW7-mediated degradation operates in normal progenitor cells to set substoichiometric levels
  13. 2022 High

    Demonstrating that ACTL6A nuclear levels increase in Schwann cells upon axonal caliber signals, leading to repressive histone mark eviction and myelination gene activation, extended the progenitor-differentiation paradigm to signal-dependent lineage commitment in the nervous system.

    Evidence Conditional KO mouse, nuclear fractionation, histone mark analysis, nerve pathology

    PMID:35434551

    Open questions at the time
    • Identity of the axonal signal that triggers ACTL6A nuclear accumulation
    • Which chromatin remodeling complex mediates histone mark eviction in Schwann cells
  14. 2023 High

    ACTL6A was shown to function as a co-transcription factor with NRF2 to activate GCLC expression and suppress ferroptosis, and separately to stabilize VPS72 and enhance MYC target gene binding, revealing transcription-factor-partnered functions beyond its classical remodeling complex roles.

    Evidence ChIP, domain deletion, ferroptosis assays for NRF2; Co-IP, protein stability, and ChIP for VPS72/MYC axis

    PMID:36631007 PMID:37443154

    Open questions at the time
    • Whether ACTL6A co-activator function with NRF2 requires BAF complex association
    • Structural basis of the ACTL6A hydrophobic region in co-transcription factor activity
  15. 2025 Medium

    Integrated multi-omics confirmed that ACTL6A depletion opens chromatin at KLF4-bound sites where SWI/SNF and INO80 cooperate to activate p53 pathway genes, while parallel studies identified ACTL6A partnerships with BACH1, BAP18/PAF1, and Sox2 at distinct gene programs, solidifying ACTL6A as a versatile chromatin gatekeeper.

    Evidence ATAC-seq/ChIP-seq/RNA-seq in CRC; Co-IP and ChIP-seq for BACH1 in ESCC; Co-IP and reporter for BAP18/PAF1 in NSCLC; Co-IP and RIP for Sox2/FTO m6A axis in SCI

    PMID:39875055 PMID:40818609 PMID:40877226 PMID:41059410

    Open questions at the time
    • How ACTL6A selects among its many transcription factor partners at specific loci
    • Whether ACTL6A operates as a true co-activator independently of remodeling ATPase activity
    • In vivo validation of FTO-mediated m6A regulation of ACTL6A mRNA

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include the structural basis for how ACTL6A dosage within BAF complexes switches between progenitor maintenance and differentiation, the relative contributions of ACTL6A to SWI/SNF versus INO80 versus NuA4/TIP60 in mammalian cells, and whether ACTL6A's co-transcription factor activities are separable from its chromatin remodeling complex functions.
  • No high-resolution structure of mammalian ACTL6A within a full BAF or INO80 complex showing dosage-dependent conformational changes
  • No systematic separation of ACTL6A contributions across its multiple resident complexes in the same cell type
  • No in vivo genetic separation of co-transcription factor versus remodeling complex functions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0008092 cytoskeletal protein binding 2 GO:0042393 histone binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005694 chromosome 2
Pathway
R-HSA-4839726 Chromatin organization 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
ACTBFBXW7KAT5NANOGSMARCA4SOX2TP53VPS72
Complex memberships
INO80NuA4/TIP60-p400SWI/SNF (BAF)SWR1

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The yeast ACTL6A ortholog Act3p/Arp4 binds to core histones via its insertion II domain (a loop-like structure unique to Arp4), as demonstrated by Far Western blot, two-hybrid analyses, and co-immunoprecipitation with histone H2A, and conditional act3 mutations affect chromatin structure of episomal DNA. Far Western blot, two-hybrid assay, co-immunoprecipitation, chromatin structure assay Molecular biology of the cell High 10436015
2002 Yeast Act3p/Arp4 (ACTL6A ortholog) is physically bound to the his4-912delta promoter in vivo and its loss reduces Act3p/Arp4 chromatin binding and alters nuclease sensitivity, establishing its direct role in transcriptional regulation through chromatin organization. Chromatin immunoprecipitation (ChIP), conditional mutation analysis, nuclease sensitivity assay Nucleic acids research High 11937627
2004 The fission yeast ACTL6A ortholog Alp5 forms a complex with Mst1-HAT (histone acetyltransferase) and is required for histone H4 acetylation at lysines 5, 8, and 12; loss of Alp5 causes kinetochore-spindle attachment defects and transcriptional desilencing at centromeres, rescued by HDAC inhibition. Immunoblotting with acetyl-histone antibodies, genetic epistasis (HDAC inhibitor rescue, clr6 double mutant), spindle checkpoint analysis (Mad2/Bub1 localization) Molecular biology of the cell High 15483052
2007 Yeast Arp4 (ACTL6A ortholog) associates with centromeric and telomeric chromatin throughout the cell cycle, and arp4 temperature-sensitive mutants show impaired kinetochore assembly (reduced Cse4p, Mtw1p, Ctf3p association) and G2/M arrest, placing Arp4 in the INO80, NuA4, and SWR1 complexes at centromeres. ChIP, conditional mutation analysis, microtubule sensitivity assay, kinetochore component localization Nucleic acids research High 17452364
2007 Yeast Arp4 (ACTL6A ortholog) directly binds to the histone acetyltransferase Esa1p (catalytic subunit of NuA4), whereas conventional actin (Act1p), also a NuA4 component, does not; this interaction does not require Arp4's specific insertions I or II. Direct protein binding assay (in vitro), deletion mutant analysis Journal of biochemistry Medium 17395615
2012 Human Arp4/BAF53/ACTL6A forms a heterocomplex with β-actin; mutations in Arp4 that reduce β-actin binding also impair incorporation into Brg1-containing SWI/SNF complexes, Myc-associated complexes, and Tip60 HAT complexes, and depletion of Arp4 accelerates Brg1 degradation and impairs complex integrity. RNA interference, co-immunoprecipitation, site-directed mutagenesis, complex integrity assay Journal of cell science High 22573825
2012 Conditional deletion of BAF53a/ACTL6A in hematopoietic stem cells causes multilineage bone marrow failure, aplastic anemia, and lethality due to a cell-autonomous proliferative impairment of HSCs and progenitors, establishing ACTL6A as essential for adult hematopoiesis. Conditional knockout mouse, hematopoietic chimera transplantation, flow cytometry, survival analysis Blood High 23018638
2013 ACTL6A prevents SWI/SNF complex binding to promoters of KLF4 and other differentiation genes in epidermal progenitors; conditional loss of ACTL6A leads to terminal differentiation and cell-cycle exit, while ectopic expression promotes the progenitor state, and SWI/SNF catalytic subunits are required for full KLF4 target induction. Conditional knockout mouse, ChIP, ectopic expression, gene expression profiling Cell stem cell High 23395444
2013 BAF53a/ACTL6A transcript is a direct target of miR-206 in rhabdomyosarcoma; sustained BAF53a expression blocks myogenic differentiation, and its silencing increases myogenic markers, inhibits proliferation, and impairs anchorage-independent growth and tumor growth. miRNA targeting assay, RNAi knockdown, differentiation assays, tumor growth assay Oncogene Medium 23728344
2015 Actl6a interacts with Nanog and Sox2 in mouse ESCs, promotes Nanog binding to pluripotency gene promoters (Oct4, Sox2), and targets promoters of key primitive endoderm regulators (Sall4, Fgf4) to repress their expression; an Actl6a mutant with impaired Tip60/p400 binding fails to block primitive endoderm differentiation. Co-immunoprecipitation, ChIP, RNAi knockdown, ectopic expression, mutant rescue assay Stem cells High 25802002
2017 Baf53a/ACTL6A interacts with Oct3/4 in mouse ES cells; conditional KO of Baf53a suppresses cell growth, increases p53, p21, and cleaved caspase-3 expression; this cell death phenotype is rescued by ectopic Baf53a (but not the E388A/R389A/R390A mutant) or by Baf53b, establishing a specific domain requirement for ESC survival. Co-immunoprecipitation, conditional tetracycline-inducible KO, Western blot, rescue with mutant constructs Scientific reports Medium 29070872
2018 Actl6a promotes histone acetylation in pluripotent stem cells in an ATP-dependent manner; higher mitochondrial ATP levels increase Actl6a expression and histone acetylation, and Actl6a knockdown reduces ESC pluripotency that cannot be rescued by exogenous ATP. Actl6a knockdown/overexpression, histone acetylation assay, ATP manipulation (rotenone treatment) FASEB journal Medium 29222327
2018 ACTL6A interacts with p53 and is co-localized with Sox2 in acute promyelocytic leukemia cells; ACTL6A knockdown promotes granulocytic differentiation and decreases Sox2 and Notch1 levels; p53 activation (by CBL0137) decreases ACTL6A expression, indicating p53 regulates ACTL6A and differentiation through physical interaction. Co-immunoprecipitation, co-localization, RNAi knockdown, pharmacological p53 activation Cellular signalling Medium 30448346
2018 The Arp8 N-terminus, Arp4 (ACTL6A ortholog) C-terminus, and HSA domain of Ino80 bind extranucleosomal DNA 37-51 bp from the nucleosome edge and function as a DNA-length sensor; disrupting Arp8-Arp4 DNA binding uncouples ATP hydrolysis from nucleosome mobilization by disengaging Arp5 from the H2A-H2B acidic patch. DNA binding assays, mutagenesis, nucleosome sliding assays, biochemical reconstitution Nature communications High 30120252
2019 ACTL6A regulates PGK1 expression in ovarian cancer cells; enforced ACTL6A expression increases PGK1, knockdown decreases it, and ACTL6A mediates FSH-enhanced glycolysis (glucose utilization, lactate production, pyruvate levels) through PGK1 downstream of the PI3K/AKT pathway. RNAi knockdown, ectopic expression, glucose metabolism assays, Western blot, in vivo xenograft Cell death & disease Medium 31649264
2020 The long non-coding RNA uc.291 physically interacts with ACTL6A and modulates its inhibitory function on BAF complex targeting; upon uc.291 depletion, ACTL6A remains bound to differentiation gene promoters and inhibits BAF complex-mediated induction of epidermal differentiation genes. ChIP, RNA-protein interaction assay, loss-of-function in primary keratinocytes and 3D skin equivalents EMBO reports Medium 32017402
2020 ACTL6A knockdown in glioma cells suppresses AKT phosphorylation and inhibits migration; pharmacological AKT activation (SC79) partly rescues the migration defect of ACTL6A-depleted cells, placing ACTL6A upstream of AKT signaling in glioma cell migration. RNAi knockdown, migration assay, Western blot, pharmacological rescue Experimental and therapeutic medicine Low 33456542
2020 HIF-1α regulates Actl6a expression and histone H3K9 acetylation in human iPSCs; Actl6a knockdown reduces H3K9ac and pluripotency and promotes endoderm differentiation, establishing an HIF-1α/Actl6a/H3K9ac axis for pluripotency maintenance. siRNA knockdown, Western blot, embryoid body/teratoma assay, histone acetylation assay FASEB journal Medium 32112486
2020 ACTL6A acts as a suppressor of nuclear F-actin formation; Arp4/ACTL6A knockdown increases nuclear F-actin in NIH3T3 cells, and purified Arp4 potently inhibits F-actin formation in mouse nuclei transplanted into Xenopus oocytes; Arp4 KD also facilitates F-actin-inducible gene expression and DNA damage repair. Protein knockdown, purified protein inhibition assay in Xenopus oocyte nuclear transplant, nuclear F-actin imaging Cells High 32204557
2020 ACTL6A interacts with p53 DNA response elements in the p21Cip1 gene promoter to suppress p21Cip1 promoter activity, mRNA, and protein levels in a p53-independent manner; elevated p21Cip1 upon ACTL6A knockdown is required for suppression of the SCC phenotype. ChIP, promoter reporter assay, RNAi knockdown, rescue experiments Oncogene Medium 32616890
2020 ACTL6A inhibition increases YAP phosphorylation and downregulates YAP-mediated transcriptional activity in cervical cancer cells, and ACTL6A restoration or YAP reactivation abrogates the antitumor effect of miR-216a-3p targeting ACTL6A. Western blot, luciferase reporter, functional rescue assays, miRNA targeting validation Journal of cellular physiology Low 32401366
2021 ACTL6A overexpression increases repair of cisplatin-DNA adducts through the SWI/SNF chromatin remodeling complex; depletion of ACTL6A inhibits cisplatin-induced DNA lesion repair and increases cisplatin sensitivity, and HDAC inhibitor treatment reverses the effect of ACTL6A overexpression on repair and cisplatin resistance in xenograft models. DNA adduct repair assay, RNAi knockdown, overexpression, HDAC inhibitor treatment, xenograft model PNAS High 33408251
2021 ACTL6A overexpression leads to stoichiometric assembly into BAF complexes, enhancing polycomb opposition genome-wide and facilitating co-dependent loading of BAF and TEAD-YAP complexes on chromatin at SCC-specific regulatory regions; in normal cells ACTL6A is substoichiometric to other BAF subunits. ATAC-seq, ChIP-seq, ectopic expression, SCC cell line studies, quantitative proteomic analysis of complex composition Molecular cell High 34687603
2021 ACTL6A interacts with p53 and Sp1 binding DNA response elements in the p21Cip1 gene promoter in mesothelioma cells, suppresses p21Cip1 promoter activity, and ACTL6A knockout reduces tumor formation with elevated p21Cip1 in vivo. ChIP, promoter reporter assay, ACTL6A KO, in vivo tumor model Oncogenesis Medium 34689163
2022 ACTL6A knockdown impairs DNA replication initiation in glioblastoma cells and transcriptionally regulates MCM5 expression; ACTL6A loss decreases CMG complex gene expression, induces DNA damage, and diminishes ATR-Chk1 pathway activity leading to apoptosis. RNAi knockdown, DNA replication assay, gene expression analysis, Western blot for ATR-Chk1 pathway Biochemical and biophysical research communications Medium 35182941
2022 ACTL6A is ubiquitinated and degraded by the E3 ubiquitin ligase FBXW7; FBXW7 interacts with ACTL6A (identified by co-immunoprecipitation and co-localization), and in vivo ubiquitination assay shows FBXW7 represses HCC malignancy through ACTL6A ubiquitin-dependent degradation. Co-immunoprecipitation, co-localization, in vivo ubiquitination assay Stem cells international Medium 36159747
2022 ACTL6A interacts with P63 in colorectal cancer cells; the BAF53A-P63 complex decreases DUSP5 expression, subsequently promoting ERK1/2 phosphorylation and cancer cell proliferation. Co-immunoprecipitation, Western blot, gene expression analysis, loss-of-function Cell death & disease Medium 36526622
2022 ACTL6A in Schwann cells integrates axonal caliber recognition signals with myelination transcriptional programs; nuclear levels of ACTL6A increase upon contact with large-caliber axons or nanofibers, leading to eviction of repressive histone marks to facilitate myelination; ACTL6A knockout mice display defective radial sorting, hypomyelination of large axons, and motor phenotype. Conditional knockout mouse, immunofluorescence/nuclear fractionation showing ACTL6A nuclear accumulation, histone mark analysis, in vivo nerve pathology iScience High 35434551
2023 ACTL6A acts as a co-transcription factor with NRF2 to upregulate GCLC (glutamate-cysteine ligase catalytic subunit) expression; the hydrophobic region of ACTL6A is required for this function, and ACTL6A upregulation of GCLC reduces ROS levels and inhibits ferroptosis in gastric cancer cells. Co-transcription factor assay, domain deletion analysis, ROS measurement, ferroptosis assay, ChIP Nature communications High 37443154
2023 VPS72 interacts with ACTL6A and MYC to form an ACTL6A/MYC complex; ACTL6A stabilizes VPS72 protein by weakening the interaction between VPS72 and the E3 ligase TRIM21, and the ACTL6A/VPS72/MYC complex enhances MYC binding to target gene promoters to promote HCC progression. Co-immunoprecipitation, protein stability assay, ChIP, AAV-shRNA in vivo knockdown Hepatology Medium 36631007
2025 ACTL6A depletion in colorectal cancer cells enhances KLF4 binding at newly accessible chromatin regions, where KLF4 cooperates with SWI/SNF and INO80 complexes to activate P53 pathway-related genes and induce apoptosis; ACTL6A normally inhibits KLF4-mediated transcriptional activation of tumor-suppressive genes. Multi-omics (ATAC-seq, ChIP-seq, RNA-seq), ACTL6A KD, KLF4 ChIP Cell death & disease High 40877226
2025 BAP18 recruits ACTL6A and PAF1 to Wnt target gene promoters to enhance β-catenin-mediated transcription in NSCLC; ACTL6A participates in a transcriptional coactivator complex with BAP18 and PAF1. Co-immunoprecipitation, luciferase reporter assay, ChIP Journal of biological chemistry Medium 40818609
2025 BAF53A/ACTL6A collaborates with BACH1 to transcriptionally activate GCLM (glutamate-cysteine ligase modifier subunit) in esophageal squamous cell carcinoma; BAF53A-BACH1 interaction identified by co-immunoprecipitation and ChIP-seq; GCLM overexpression rescues redox balance in BAF53A- or BACH1-silenced cells. Co-immunoprecipitation, ChIP-seq, GCLM rescue experiment, ROS and GSH/GSSG measurement PeerJ Medium 41059410
2025 Actl6a regulates autophagy in spinal cord injury by cooperating with Sox2 to upregulate Atg5 and Atg7 expression; Fto modulates Actl6a mRNA stability via m6A demethylation, and Actl6a overexpression enhances autophagy and reduces apoptosis in SCI models. Co-immunoprecipitation (Actl6a-Sox2 interaction), m6A dot blot, RNA immunoprecipitation, in vivo SCI model (AAV), Western blot Journal of advanced research Medium 39875055
2025 ACTL6A mediates chromatin accessibility at AP-1 transcription factor sites and regulates upstream MAPK signaling through induction of Ras and Galectin-1, thereby driving aerobic glycolysis (Warburg effect) and blunting HIF1α/HIF2α induction in HNSCC; ACTL6A knockdown induces mitochondrial dependency. ATAC-seq, RNAi knockdown, metabolic flux assays (glycolysis/OXPHOS), in vivo treatment with complex I inhibitor bioRxivpreprint Medium 40950224

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The nuclear actin-related protein of Saccharomyces cerevisiae, Act3p/Arp4, interacts with core histones. Molecular biology of the cell 107 10436015
2013 ACTL6a enforces the epidermal progenitor state by suppressing SWI/SNF-dependent induction of KLF4. Cell stem cell 102 23395444
2012 The BAF53a subunit of SWI/SNF-like BAF complexes is essential for hemopoietic stem cell function. Blood 102 23018638
2023 ACTL6A protects gastric cancer cells against ferroptosis through induction of glutathione synthesis. Nature communications 89 37443154
2021 ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer. Proceedings of the National Academy of Sciences of the United States of America 67 33408251
2018 The Arp8 and Arp4 module acts as a DNA sensor controlling INO80 chromatin remodeling. Nature communications 64 30120252
2013 Failure to downregulate the BAF53a subunit of the SWI/SNF chromatin remodeling complex contributes to the differentiation block in rhabdomyosarcoma. Oncogene 50 23728344
2019 ACTL6A regulates follicle-stimulating hormone-driven glycolysis in ovarian cancer cells via PGK1. Cell death & disease 44 31649264
2015 Actl6a protects embryonic stem cells from differentiating into primitive endoderm. Stem cells (Dayton, Ohio) 44 25802002
2012 Heterocomplex formation by Arp4 and β-actin is involved in the integrity of the Brg1 chromatin remodeling complex. Journal of cell science 41 22573825
2018 ACTL6A expression promotes invasion, metastasis and epithelial mesenchymal transition of colon cancer. BMC cancer 40 30348114
2021 Increased ACTL6A occupancy within mSWI/SNF chromatin remodelers drives human squamous cell carcinoma. Molecular cell 36 34687603
2020 Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex. EMBO reports 35 32017402
2002 Correlation between chromatin association and transcriptional regulation for the Act3p/Arp4 nuclear actin-related protein of Saccharomyces cerevisiae. Nucleic acids research 35 11937627
2004 BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation, kinetochore-spindle attachment, and gene silencing at centromere. Molecular biology of the cell 32 15483052
2020 MiR-216a-3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A-mediated YAP signaling. Journal of cellular physiology 28 32401366
2017 Heterozygous variants in ACTL6A, encoding a component of the BAF complex, are associated with intellectual disability. Human mutation 27 28649782
2007 Actin-related protein Arp4 functions in kinetochore assembly. Nucleic acids research 27 17452364
2020 ACTL6A suppresses p21Cip1 expression to enhance the epidermal squamous cell carcinoma phenotype. Oncogene 25 32616890
2023 Targeting VPS72 inhibits ACTL6A/MYC axis activity in HCC progression. Hepatology (Baltimore, Md.) 24 36631007
2020 HIF-1α/Actl6a/H3K9ac axis is critical for pluripotency and lineage differentiation of human induced pluripotent stem cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20 32112486
2022 BAF53A drives colorectal cancer development by regulating DUSP5-mediated ERK phosphorylation. Cell death & disease 18 36526622
2018 Mitochondrially produced ATP affects stem cell pluripotency via Actl6a-mediated histone acetylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 29222327
2018 ACTL6A interacts with p53 in acute promyelocytic leukemia cell lines to affect differentiation via the Sox2/Notch1 signaling pathway. Cellular signalling 18 30448346
2017 Baf53a is involved in survival of mouse ES cells, which can be compensated by Baf53b. Scientific reports 18 29070872
2008 The nuclear actin-related protein Act3p/Arp4 influences yeast cell shape and bulk chromatin organization. Journal of cellular biochemistry 17 18004728
2020 The Actin-Family Protein Arp4 Is a Novel Suppressor for the Formation and Functions of Nuclear F-Actin. Cells 14 32204557
2022 FBXW7 Reduces the Cancer Stem Cell-Like Properties of Hepatocellular Carcinoma by Regulating the Ubiquitination and Degradation of ACTL6A. Stem cells international 11 36159747
2022 ACTL6A deficiency induces apoptosis through impairing DNA replication and inhibiting the ATR-Chk1 signaling in glioblastoma cells. Biochemical and biophysical research communications 10 35182941
2021 ACTL6A promotes the growth in non-small cell lung cancer by regulating Hippo/Yap pathway. Experimental lung research 9 33896314
2021 ACTL6A Promotes the Proliferation of Esophageal Squamous Cell Carcinoma Cells and Correlates with Poor Clinical Outcomes. OncoTargets and therapy 8 33469301
2022 ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve. iScience 7 35434551
2020 ACTL6A knockdown inhibits cell migration by suppressing the AKT signaling pathway and enhances the sensitivity of glioma cells to temozolomide. Experimental and therapeutic medicine 7 33456542
2006 Novel regulatory properties of Saccharomyces cerevisiae Arp4. Journal of biochemistry 7 16672275
2024 Sulforaphane suppresses cell proliferation and induces apoptosis in glioma via the ACTL6A/PGK1 axis. Toxicology mechanisms and methods 5 38221767
2021 MicroRNA-543 inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of triple-negative breast cancer cells via down-regulation of ACTL6A gene. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 5 34181232
2021 ACTL6A suppresses p21Cip1 tumor suppressor expression to maintain an aggressive mesothelioma cancer cell phenotype. Oncogenesis 4 34689163
2020 The p.Arg377Trp variant in ACTL6A underlines a recognizable BAF-opathy phenotype. Clinical genetics 4 31994175
2007 The nuclear actin-related protein of Saccharomyces cerevisiae, Arp4, directly interacts with the histone acetyltransferase Esa1p. Journal of biochemistry 4 17395615
2000 Further characterization of the actin-related protein Act3p/Arp4 of S. cerevisiae through mutational analysis. Molecular biology reports 3 10939524
2025 Actl6a regulates autophagy via Sox2-dependent Atg5 and Atg7 expression to inhibit apoptosis in spinal cord injury. Journal of advanced research 2 39875055
2025 A multimodal approach for establishing ACTL6A and ERCC1 as chemoresistance genes in locally advanced head and neck cancer. Frontiers in pharmacology 1 40510426
2025 ACTL6A depletion induces KLF4-mediated anti-tumorigenic effects in colorectal cancer. Cell death & disease 1 40877226
2021 Case Report: BAF-Opathies/SSRIDDs Due to a de novo ACTL6A Variant, Previously Considered to Be Heart-Hand Syndrome. Frontiers in cardiovascular medicine 1 34485408
1992 Temperature-sensitive immunoglobulin A-binding and dimerization of C-terminus-impaired protein Arp4 produced in Escherichia coli. Microbiology and immunology 1 1461150
2025 Unveiling the role of ACTL6A in uveal melanoma metastasis and immune microenvironment. International immunopharmacology 0 39746274
2025 Emerging Roles of ACTL6A as an Oncogenic Hub: Transcriptional Regulation and Beyond. Molecular cancer research : MCR 0 40192597
2025 The chromatin remodeling factor BAP18 promotes non-small cell lung cancer progression via the recruitment of β-catenin with the transcriptional coactivator complex ACTL6A-PAF1. The Journal of biological chemistry 0 40818609
2025 ACTL6A regulates the Warburg effect through coordinated activation of AP-1 signaling in head and neck squamous cell carcinoma. bioRxiv : the preprint server for biology 0 40950224
2025 The BAF53A-BACH1-GCLM axis regulates glutathione metabolism and enhances ferroptosis resistance in esophageal squamous cell carcinoma. PeerJ 0 41059410
2025 The Knockdown of ACTL6A Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma by Modulating the Wnt/β-Catenin Signaling Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41137713
2025 ACTL6A accelerates the progression of NSCLC through hippo/YAP signaling axis and TAMs-mediated immune regulation. International immunopharmacology 0 41223612