Affinage

ACIN1

Apoptotic chromatin condensation inducer in the nucleus · UniProt Q9UKV3

Length
1341 aa
Mass
151.9 kDa
Annotated
2026-04-28
98 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACIN1 (Acinus) is a nuclear RNA-binding protein that integrates apoptotic DNA fragmentation, pre-mRNA splicing regulation, and autophagy control. During apoptosis, caspase-3 cleaves ACIN1 to generate a p17 fragment that activates PKC-δ–mediated histone H2B phosphorylation, driving chromatin condensation and internucleosomal DNA fragmentation; this cleavage is antagonized by Akt phosphorylation at S422/S573 and by the anti-apoptotic protein AAC-11 (PMID:10490026, PMID:16537548, PMID:17721436, PMID:16177823, PMID:19387494). As a peripheral exon junction complex component, ACIN1 directly binds pre-mRNAs at suboptimal introns via its RRM domain to regulate alternative cassette exon inclusion—including splicing of DFFA/ICAD—and its global deletion in mice causes embryonic lethality while muscle-specific loss produces myofiber defects with widespread splicing alterations (PMID:27365209, PMID:40269054, PMID:30042883). In Drosophila, Acinus stability is controlled by a Cdk5/PPM phosphatase phosphoswitch at S437 that promotes starvation-independent basal autophagy, conferring neuroprotection against polyglutamine and Aβ42 toxicity and extending lifespan (PMID:29227247, PMID:35037620, PMID:25332163).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Identification of ACIN1 as a caspase-3-activated nuclear factor established a direct effector link between the apoptotic protease cascade and chromatin remodeling.

    Evidence In vitro chromatin condensation assay with immunodepletion and antisense knockdown in cells

    PMID:10490026

    Open questions at the time
    • Initial assignment to chromatin condensation was later revised; the specific condensation vs. DNA fragmentation role needed clarification
    • Downstream mechanism linking p17 fragment to chromatin changes was unknown
  2. 2005 High

    Demonstrating that Akt phosphorylates ACIN1 at S422/S573 to block caspase-3 cleavage revealed how survival signaling directly protects a pro-apoptotic effector from activation.

    Evidence In vitro kinase assay, phospho-mimetic/non-phosphorylatable mutagenesis, siRNA-mediated Akt depletion with chromatin condensation readout

    PMID:16177823

    Open questions at the time
    • Whether other kinases phosphorylate the same sites under different stimuli was untested
    • Functional consequence of Akt-mediated protection on DNA fragmentation specifically (vs. condensation) was not dissected
  3. 2006 High

    Inducible RNAi clarified that ACIN1 is required for apoptotic internucleosomal DNA fragmentation rather than chromatin condensation, correcting the originally proposed function.

    Evidence Stable inducible RNAi knockdown with DNA ladder analysis and cell-free condensation assay

    PMID:16537548

    Open questions at the time
    • The molecular target through which ACIN1 promotes DNA fragmentation was not identified in this study
  4. 2007 High

    Identification of PKC-δ as the effector kinase activated by the ACIN1 p17 fragment, leading to H2B phosphorylation, provided a mechanistic pathway from caspase cleavage to chromatin remodeling.

    Evidence Co-immunoprecipitation, PKC-δ knockout MEFs, dominant-negative overexpression, kinase assays

    PMID:17721436

    Open questions at the time
    • How p17 activates PKC-δ at the structural level remains undefined
    • The relationship between H2B phosphorylation and the DNA fragmentation phenotype was not resolved
  5. 2008 High

    Linking SRPK2-mediated phosphorylation of ACIN1 at S422 to cyclin A1 transcription and cell cycle progression revealed a non-apoptotic nuclear function in proliferation control.

    Evidence In vitro kinase assay, phospho-mimetic mutagenesis, siRNA, cyclin A1 transcription assays, cell cycle analysis in leukemia cells

    PMID:18559500

    Open questions at the time
    • Whether ACIN1 acts as a direct transcriptional regulator or indirectly through splicing was not distinguished
    • Convergence of Akt and SRPK2 phosphorylation at the same S422 site was not mechanistically resolved
  6. 2009 High

    Discovery that AAC-11 binds ACIN1 via its leucine-zipper domain to shield it from caspase-3 cleavage established a protein–protein interaction mechanism for apoptotic resistance, distinct from kinase-mediated protection.

    Evidence Co-immunoprecipitation, in vitro caspase cleavage assay, cell-permeable peptide competition, DNA fragmentation assay

    PMID:19387494

    Open questions at the time
    • Structural basis of AAC-11/ACIN1 interaction at atomic resolution is lacking
  7. 2010 High

    Drosophila loss-of-function studies extended ACIN1 function beyond apoptosis to endosomal trafficking and autophagy, showing dacn regulates autophagosome maturation independently of Tor.

    Evidence Drosophila genetic epistasis with Notch/Egfr/Tor pathways, autophagy and endosome assays

    PMID:20504956

    Open questions at the time
    • Conservation of the autophagy role in mammalian systems was not demonstrated
    • Molecular mechanism linking Acinus to autophagosome maturation was undefined
  8. 2014 High

    Demonstrating that AKT1-stabilized, caspase-resistant Drosophila Acinus enhances basal autophagy, reduces neurodegeneration, and extends lifespan established a phospho-regulatory switch balancing apoptotic cleavage against autophagy promotion.

    Evidence Drosophila phosphomimetic and caspase-resistant mutants, autophagy assays, Huntingtin neurodegeneration model, lifespan analysis

    PMID:25332163

    Open questions at the time
    • The specific phosphorylation site mediating autophagy was not pinpointed in this study
    • Whether the mammalian Akt-Acinus axis similarly regulates autophagy was untested
  9. 2015 High

    Identification of ACIN1 as a direct mTORC1 substrate placed it at the intersection of nutrient sensing and its known apoptosis/splicing functions, though the functional consequence of mTORC1 phosphorylation remains uncharacterized.

    Evidence Quantitative phosphoproteomics, endogenous mTOR co-immunoprecipitation, MS-enhanced in vitro kinase assay

    PMID:25907765

    Open questions at the time
    • Phosphorylation sites and downstream effects of mTORC1-mediated phosphorylation on ACIN1 function were not determined
    • Relationship between mTORC1 regulation and Acinus autophagy role was not tested
  10. 2016 High

    Genome-wide iCLIP and RNA-seq established ACIN1 as a peripheral EJC component that directly binds pre-mRNAs at suboptimal introns to regulate alternative cassette exon inclusion, unifying its splicing role with a defined RNA-binding mechanism.

    Evidence iCLIP cross-linking immunoprecipitation, siRNA depletion, RNA-seq, EJC co-immunoprecipitation

    PMID:27365209

    Open questions at the time
    • How ACIN1's RNA-binding specificity is determined at suboptimal introns was not structurally resolved
    • Whether splicing regulation by ACIN1 is functionally coupled to its apoptotic or autophagy roles was not addressed
  11. 2017 High

    Pinpointing Cdk5-mediated phosphorylation of Drosophila Acinus at S437 as the specific modification promoting basal autophagy and neuroprotection identified the molecular switch regulating Acinus stability in neurons.

    Evidence Drosophila p35/Cdk5 genetics, phospho-specific antibodies, phosphomimetic rescue, polyQ and Aβ42 neurodegeneration models

    PMID:29227247

    Open questions at the time
    • The opposing phosphatase was unknown at this point
    • Conservation of the Cdk5-Acinus axis in mammalian neurons was not tested
  12. 2018 High

    The 1.65 Å crystal structure of the ACIN1 RRM domain revealed a non-classical C-terminal α-helix occluding the RNA-binding surface that also harbors the caspase-3 cleavage site, providing a structural basis for the coupling between caspase activation and RNA-binding competence.

    Evidence X-ray crystallography at 1.65 Å resolution

    PMID:30042883

    Open questions at the time
    • No co-crystal structure with RNA was obtained
    • Whether caspase cleavage actually derepresses RNA binding in cells was not functionally validated
  13. 2022 High

    Identification of the PPM-type phosphatase Nil as the counterbalancing enzyme to Cdk5 at Acinus S437 completed the phosphoswitch model, and showed cadmium inhibits Nil to elevate autophagy, revealing an environmental input to the pathway.

    Evidence Drosophila genetic screen, nil loss-of-function mutants, phospho-S437 antibodies, Cd²⁺ exposure, autophagy and neurodegeneration assays

    PMID:35037620

    Open questions at the time
    • Mammalian ortholog of Nil and conservation of the phosphoswitch in human neurons not established
    • Whether Cd²⁺-induced autophagy via Acinus has physiological relevance in mammalian toxicology is untested
  14. 2025 High

    Global and conditional knockout in mice demonstrated that ACIN1 is essential for embryonic viability and required in skeletal muscle for proper myofiber homeostasis and splicing of muscle-disease and mitochondrial genes, providing the first mammalian genetic proof of its in vivo splicing role.

    Evidence Global knockout (lethal ~E11.5) and muscle-specific conditional knockout mice with RNA-seq splicing analysis

    PMID:40269054

    Open questions at the time
    • Tissue-specific roles beyond muscle have not been characterized by conditional deletion
    • Whether the autophagy function observed in Drosophila operates in mammalian tissues in vivo remains untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include whether the Cdk5/PPM phosphoswitch controlling autophagy is conserved in mammals, how mTORC1 phosphorylation functionally modulates ACIN1, and whether the structural coupling between caspase cleavage and RRM RNA-binding capacity regulates splicing in vivo.
  • Mammalian Cdk5-Acinus autophagy axis not demonstrated
  • Functional consequence of mTORC1 phosphorylation on ACIN1 activity unknown
  • No RNA-bound co-crystal structure to validate structural model of RRM activation by caspase cleavage

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-9612973 Autophagy 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-162582 Signal Transduction 2
Partners
AAC11AKT1CASP3PRKCDRNPS1SAP18SRPK2SRRM2
Complex memberships
ASAP complexexon junction complex (EJC)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Acinus (ACIN1) is a nuclear factor that induces apoptotic chromatin condensation after proteolytic cleavage by caspase-3, without inducing DNA fragmentation. Immunodepletion experiments established that Acinus is essential for apoptotic chromatin condensation in vitro. In vitro chromatin condensation assay, immunodepletion, antisense knockdown in cells Nature High 10490026
2005 Akt directly phosphorylates Acinus on serine 422 and serine 573 in the nucleus, making Acinus resistant to caspase-3 cleavage and thereby inhibiting apoptotic chromatin condensation. Phosphorylation-mimetic mutants (S422D/S573D) resist caspase cleavage; non-phosphorylatable mutants accelerate chromatin condensation. Akt depletion provokes apoptotic cleavage of Acinus. In vitro kinase assay, site-directed mutagenesis, siRNA knockdown, cell-based chromatin condensation assay The EMBO journal High 16177823
2006 RNAi-mediated knockdown of Acinus isoforms in stable cell lines shows that Acinus is not required for apoptotic chromatin condensation but is required for oligonucleosomal (internucleosomal) DNA fragmentation during apoptosis. Acinus is also not required for nuclear localization or interaction of ASAP complex subunits SAP18 and RNPS1. Inducible RNAi knockdown, cell-free chromatin condensation assay, DNA ladder analysis The Journal of biological chemistry High 16537548
2007 The caspase-3-cleaved Acinus p17 fragment induces apoptotic chromatin condensation by activating PKC-delta, which then phosphorylates histone H2B. Acinus p17 binds both Mst1 and PKC-delta and enhances their kinase activities; dominant-negative PKC-delta (but not Mst1) blocks Acinus-initiated H2B phosphorylation and chromatin condensation. Co-immunoprecipitation, dominant-negative overexpression, PKC-delta knockout MEFs, siRNA knockdown, kinase assays Cell death and differentiation High 17721436
2007 Akt phosphorylates zyxin on serine 142, promoting zyxin nuclear translocation (facilitated by 14-3-3γ) and its association with Acinus-S in the nucleus, thereby preventing caspase-dependent Acinus-S cleavage and chromatin condensation. Co-immunoprecipitation, site-directed mutagenesis, phosphorylation-mimetic mutants, chromatin condensation assay Cell death and differentiation Medium 17572661
2008 SRPK2 binds and phosphorylates Acinus, redistributing it from nuclear speckles to the nucleoplasm, leading to upregulation of cyclin A1 (but not A2) expression and promotion of leukemia cell proliferation. The S422D phosphorylation-mimetic Acinus enhances cyclin A1 transcription; S422A (unphosphorylatable) blocks SRPK2's stimulatory effect. Ablation of Acinus or SRPK2 arrests cells at G1. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, siRNA knockdown, cyclin A1 transcription assays, cell cycle analysis Cancer research High 18559500
2009 AAC-11 (a survival protein) directly binds Acinus via its leucine-zipper domain and protects Acinus from caspase-3 cleavage both in vivo and in vitro, thereby preventing Acinus-mediated DNA fragmentation. Disruption of AAC-11 oligomerization with a cell-permeable leucine-zipper peptide inhibits AAC-11/Acinus complex formation and potentiates apoptosis. Co-immunoprecipitation, in vitro caspase cleavage assay, siRNA depletion, cell-permeable peptide competition, DNA fragmentation assays The EMBO journal High 19387494
2009 NGF promotes interaction of transcriptional corepressor CtBP2 with Acinus through Akt-mediated Acinus phosphorylation, leading to repression of cyclin A1 expression and inhibition of leukemia cell proliferation. Co-immunoprecipitation, siRNA knockdown, cyclin A1 reporter assays, cell proliferation assays Oncogene Medium 19668232
2010 Drosophila Acinus (dacn) regulates endosomal trafficking and autophagy. Loss of dacn destabilizes early endosomes (modulating Notch and Egfr signaling) and blocks autophagosome maturation during starvation responses. Overexpression of dacn causes lethality through enhanced autophagy, independently of the Tor pathway. Drosophila loss-of-function genetics, epistasis with Notch/Egfr pathway, autophagy assays, Tor pathway analysis Development (Cambridge, England) High 20504956
2014 In Drosophila, Acinus (Acn) stability and autophagy promotion are regulated by two opposing activities: (1) AKT1-mediated phosphorylation stabilizes Acn, and (2) the caspase Dcp-1 cleaves Acn to destabilize it. Stabilized Acn (phosphomimetic S641,731D or caspase-resistant D527A mutant) enhances basal autophagy and improves starvation resistance, reduces Huntingtin-induced neurodegeneration, and prolongs lifespan. Drosophila genetics, phosphomimetic and caspase-resistant Acn mutants, autophagy assays, neurodegeneration model, lifespan analysis The Journal of cell biology High 25332163
2015 Acinus L is a direct substrate of mTORC1 (mammalian target of rapamycin complex 1) in response to insulin and amino acids. This was established by co-immunoprecipitation of endogenous mTOR with Acinus L and confirmed with MS-enhanced in vitro kinase assays. Quantitative phosphoproteomics, co-immunoprecipitation, MS-enhanced in vitro kinase assay Molecular & cellular proteomics : MCP High 25907765
2015 Acinus isoforms regulate pre-mRNA splicing in a retinoic acid (RA)-dependent and RA-independent manner. Acinus-L and Acinus-S' increase splicing of a weak 5' splice site minigene; RA further enhances this activity. The RRM domain is required for RA-dependent splicing activity. RNPS1 represses the RA-independent splicing activity of Acinus. Acinus also regulates alternative 5' splice site selection in endogenous RARβ and Bcl-x. In vivo splicing minigene assays, domain mutagenesis, endogenous splicing analysis Journal of cellular physiology Medium 25205379
2016 Acinus is a peripheral component of the exon junction complex (EJC) that directly binds pre-mRNAs at suboptimal introns and spliced mRNAs. iCLIP mapping reveals Acinus is preferentially required for inclusion of specific alternative cassette exons and faithful splicing of a subset of introns. Acinus also regulates splicing of the DFFA/ICAD transcript (a regulator of DNA fragmentation) and is involved in cell cycle gene regulation. iCLIP (cross-linking immunoprecipitation), siRNA depletion, RNA-seq, EJC co-immunoprecipitation RNA (New York, N.Y.) High 27365209
2017 In Drosophila, Cdk5 phosphorylates Acinus at serine 437, stabilizing Acn and promoting starvation-independent basal autophagy. Loss of Cdk5 or its cofactor p35 reduces pS437-Acn phosphorylation and basal autophagy and shortens lifespan. Expression of stabilized phosphomimetic AcnS437D restores basal autophagy and lifespan in p35 mutants and is required for protective responses to polyQ proteins and Aβ42. Drosophila gain/loss-of-function genetics, phospho-specific antibodies, autophagy assays, neurodegeneration models, phosphomimetic mutagenesis eLife High 29227247
2014 The sub-nuclear localization of Acinus isoforms is determined by their structural domains: the SAP motif of Acinus-L directs diffuse nucleoplasmic localization, while the C-terminal RS- and RD/E-rich region of Acinus-S' directs localization to nuclear speckles (colocalizing with SC35). The C-terminal RS/RD/E-rich region also mediates Acinus-RNPS1 colocalization. Fluorescence microscopy, domain deletion/mutation analysis, colocalization with nuclear speckle marker SC35 Journal of cellular biochemistry Medium 25079509
2018 Crystal structure of the human Acinus RRM domain determined at 1.65 Å resolution. The structure shows a classical four-stranded antiparallel β-sheet with two flanking α-helices plus a non-classical C-terminal α-helix that occludes the potential RNA-binding surface of the β-sheet and harbors the caspase-3 cleavage site. This C-terminal helix must change conformation to enable RNA binding. X-ray crystallography at 1.65 Å resolution PeerJ High 30042883
2019 ACIN1 forms a recurrent ACIN1-NUTM1 gene fusion in infant acute lymphoblastic leukemia. Two isoforms of the fusion join exons 3 or 4 of ACIN1 to exon 3 of NUTM1, with both retaining the functional SAP domain of ACIN1. Transcriptome sequencing, RT-PCR validation, cytogenetic analysis Genes, chromosomes & cancer Medium 31515871
2019 The arginine/serine (RS) and RNPS1-SAP18-binding (RSB) domains of Acinus regulate alternative splice site selection when tethered to a reporter, stimulating alternative splicing. Full-length Acinus-S' does not modulate splice site selection in the HIV-1 minigene system, indicating domain-specific roles. In vivo splicing minigene assays, domain tethering Cell biology international Low 31070279
2020 The SRSF3-MBNL1-Acin1 axis regulates DNA fragmentation in colorectal cancer via alternative splicing: upregulated SRSF3 promotes inclusion of MBNL1 exons 5 and 7, producing the MBNL18 isoform which shifts Acin1 splicing from the Acin1-S isoform to the Acin1-L isoform, resulting in diminished DNA fragmentation under oxidative stress. Transcriptome analysis, splicing assays, siRNA depletion, isoform overexpression, apoptosis assays Neoplasia (New York, N.Y.) Medium 33142236
2020 Acin1 isoforms (Acin1-L and Acin1-S) have discriminative influences on brown adipogenesis and regulate SRSF3 expression through an alternative splicing-coupled nonsense-mediated decay mechanism. Depletion of endogenous Acin1 activates brown adipogenic signatures, and the Acin1-SRSF3 axis participates in the brown adipocyte-related splicing network. siRNA depletion, isoform overexpression, RNA-seq, splicing assays, brown adipogenesis assays Biochimica et biophysica acta. Gene regulatory mechanisms Medium 32629174
2022 In Drosophila, the PPM-type phosphatase Nil (CG6036) counterbalances Cdk5-dependent phosphorylation of Acinus at serine 437. Loss of nil enhances pS437-Acn levels, elevates neuronal autophagy, reduces polyQ protein accumulation. Cadmium (Cd2+) exposure elevates acn-S437 phosphorylation by inhibiting Nil phosphatase, increasing neuronal autophagy and protecting against Cd2+-induced cytotoxicity. Drosophila genetic screen, loss-of-function mutants, phospho-specific antibodies, autophagy assays, Huntington's disease model, Cd2+ exposure eLife High 35037620
2025 Global deletion of Acin1 in mice causes embryonic lethality around E11.5, with developmental delays and increased apoptosis, establishing Acin1 as essential for embryonic development. Skeletal muscle-specific conditional knockout (Acin1 MKO) mice show enlarged myofibers, ongoing muscle damage/regeneration, and altered splicing of genes associated with muscle disease and mitochondrial function. Global and conditional (muscle-specific) knockout mice, RNA-seq for expression and splicing analysis Scientific reports High 40269054
2025 A point mutation in SRRM2 associated with ALS leads to loss of the SRRM2-ACIN1 protein-protein interaction, linking ACIN1 to the nuclear speckle/splicing machinery relevant to neurodegeneration. Cell line endogenous gene editing, protein-protein interaction analysis bioRxivpreprint Low bio_10.1101_2025.09.11.675713

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature 361 10490026
2013 SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 137 23558573
1993 Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. The Journal of biological chemistry 112 8349710
1989 Hepatic enzymic zonation: a reevaluation of the concept of the liver acinus. Hepatology (Baltimore, Md.) 110 2472341
2018 A glass-based, continuously zonated and vascularized human liver acinus microphysiological system (vLAMPS) designed for experimental modeling of diseases and ADME/TOX. Lab on a chip 106 30063238
1987 Pulmonary acinus: geometry and morphometry of the peripheral airway system in rat and rabbit. The American journal of anatomy 96 3673919
1988 Complementary distribution of carbamoylphosphate synthetase (ammonia) and glutamine synthetase in rat liver acinus is regulated at a pretranslational level. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 95 2898495
1992 Connexins and glucagon receptors during development of rat hepatic acinus. The American journal of physiology 84 1332499
2005 Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation. The EMBO journal 78 16177823
1992 Metabolic heterogeneity of hepatocytes across the liver acinus. The Journal of nutrition 78 1542056
2008 Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1. Cancer research 74 18559500
2009 The antiapoptotic protein AAC-11 interacts with and regulates Acinus-mediated DNA fragmentation. The EMBO journal 64 19387494
1982 Reciprocal distribution of hexokinase and glucokinase in the periportal and perivenous zone of the rat liver acinus. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 61 7076132
1981 Salivary gland of the tick vector (R. appendiculatus) of East Coast fever. I. Ultrastructure of the type III acinus. Tissue & cell 49 7198303
2021 Arabidopsis ACINUS is O-glycosylated and regulates transcription and alternative splicing of regulators of reproductive transitions. Nature communications 46 33574257
1986 The isolation of functionally heterogeneous hepatocytes of the proximal and distal half of the liver acinus in the rat. Hepatology (Baltimore, Md.) 45 3019862
2006 Loss of Acinus inhibits oligonucleosomal DNA fragmentation but not chromatin condensation during apoptosis. The Journal of biological chemistry 44 16537548
1983 Functional and anatomic heterogeneity in the liver acinus: impact on transport. The American journal of physiology 44 6859265
1987 Development of the pulmonary acinus in fetal rat lung: a study based on an antiserum recognizing surfactant-associated proteins. Anatomy and embryology 41 3548484
1981 Salivary gland of the tick vector (R. appendiculatus) of East Coast fever. II. Cellular basis for fluid secretion in the type III acinus. Tissue & cell 41 7198304
2007 Akt phosphorylation of zyxin mediates its interaction with acinus-S and prevents acinus-triggered chromatin condensation. Cell death and differentiation 40 17572661
1994 Endothelial cell heterogeneity in the normal human liver acinus: in situ immunohistochemical demonstration. Liver 38 8078390
2016 The RNA-binding profile of Acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA (New York, N.Y.) 37 27365209
2000 A three-dimensional model of the human pulmonary acinus. Journal of applied physiology (Bethesda, Md. : 1985) 35 10846044
2020 Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS). Toxicology 33 33307106
2017 Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437. eLife 32 29227247
2001 Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion. Pflugers Archiv : European journal of physiology 30 11374055
1994 Alveolar epithelial composition and architecture of the late fetal pulmonary acinus: an immunocytochemical and morphometric study in a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia. Experimental lung research 30 7882903
1989 Induction of P-450IIB genes within the rat liver acinus is not dependent on the chemical inducer or on the acinar organization. The Journal of biological chemistry 30 2470762
1989 In situ kinetic parameters of glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase in different areas of the rat liver acinus. The Histochemical journal 29 2592252
2010 PKCzeta regulates cell polarisation and proliferation restriction during mammary acinus formation. Journal of cell science 28 20844151
1996 The location of hepatocytes in the rat liver acinus determines their sensitivity to calcium-mobilizing hormones. Gastroenterology 28 8898649
2019 Mechanical Stabilization of the Glandular Acinus by Linker of Nucleoskeleton and Cytoskeleton Complex. Current biology : CB 27 31402305
2019 Cryptic recurrent ACIN1-NUTM1 fusions in non-KMT2A-rearranged infant acute lymphoblastic leukemia. Genes, chromosomes & cancer 27 31515871
2005 Diffusion-reaction in branched structures: theory and application to the lung acinus. Physical review letters 27 15783623
2010 Drosophila acinus encodes a novel regulator of endocytic and autophagic trafficking. Development (Cambridge, England) 26 20504956
2005 Ultrastructural zonal heterogeneity of hepatocytes and mitochondria within the hepatic acinus during liver regeneration after partial hepatectomy. Biology of the cell 26 15762849
1993 Ultrastructural features of alveolar epithelial cells in the late fetal pulmonary acinus: a comparison between normal and hypoplastic lungs using a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia. Microscopy research and technique 26 8286785
1986 Heterogeneous expression of phenobarbital-inducible cytochrome P-450 genes within the hepatic acinus in the rat. Hepatology (Baltimore, Md.) 26 3758946
1999 Distribution of alcohol dehydrogenase isoenzymes in the human liver acinus. Histochemistry and cell biology 24 10403118
2007 Acinus-provoked protein kinase C delta isoform activation is essential for apoptotic chromatin condensation. Cell death and differentiation 23 17721436
2009 NGF inhibits human leukemia proliferation by downregulating cyclin A1 expression through promoting acinus/CtBP2 association. Oncogene 22 19668232
1987 Primary culture of epithelial cells derived from the rat ventral prostate: formation of three-dimensional acinus-like structure in collagen gel. The Prostate 22 3562346
2015 Epstein-Barr virus latent membrane protein 2 induces autophagy to promote abnormal acinus formation. Journal of virology 21 25878108
2013 A microfluidic device mimicking acinar concentration gradients across the liver acinus. Biomedical microdevices 21 23563756
2022 Liver Acinus Dynamic Chip for Assessment of Drug-Induced Zonal Hepatotoxicity. Biosensors 18 35884248
2018 Measuring Hypopharyngeal Gland Acinus Size in Honey Bee (Apis mellifera) Workers. Journal of visualized experiments : JoVE 18 30272666
2014 Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy. The Journal of cell biology 18 25332163
1998 Transient swelling of salivary acinus induced by acetylcholine stimulation: water secretion pathway in rat submandibular gland. The Journal of membrane biology 18 9493134
2015 Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Substrate. Molecular & cellular proteomics : MCP 17 25907765
2013 Chronic low-dose radiation inhibits the cells death by cytotoxic high-dose radiation increasing the level of AKT and acinus proteins via NF-κB activation. International journal of radiation biology 17 23205493
1997 Reconstruction of prostatic acinus-like structure from ventral and dorsolateral prostatic epithelial cells of the rat in three-dimensional collagen gel matrix culture. The Journal of urology 17 9072537
2015 Role of Acinus in regulating retinoic acid-responsive gene pre-mRNA splicing. Journal of cellular physiology 16 25205379
2013 Increased extracellular matrix density decreases MCF10A breast cell acinus formation in 3D culture conditions. Journal of tissue engineering and regenerative medicine 16 23404906
2012 Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies. The Journal of membrane biology 16 22258315
2023 Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem. Microsystems & nanoengineering 14 37303831
2018 [Expression and Significance of ACIN1 mRNA in Platelets of Lung Cancer]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 14 30201066
2006 The ACIN1 gene is hypermethylated in early stage lung adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 14 17409846
1998 Ca2+ signaling in the pancreatic acinus. Pancreas 13 9548666
1984 Microbiochemical investigation on diurnal rhythmic changes of the activities of the lactate dehydrogenase in the periportal and perivenous zones of the acinus of the rat liver. Histochemistry 13 6542909
2020 The SRSF3-MBNL1-Acin1 circuit constitutes an emerging axis to lessen DNA fragmentation in colorectal cancer via an alternative splicing mechanism. Neoplasia (New York, N.Y.) 12 33142236
2006 Small Rho GTPases are important for acinus formation in a human salivary gland cell line. Cell and tissue research 12 16639616
1976 DNA synthesis and cell proliferation in the simple liver acinus of 10 to 20-day-old rats: evidence for cell fusion. The Anatomical record 12 943970
2018 Cdk5-mediated Acn/Acinus phosphorylation regulates basal autophagy independently of metabolic stress. Autophagy 11 29782227
2020 Altered expressions and splicing profiles of Acin1 transcripts differentially modulate brown adipogenesis through an alternative splicing mechanism. Biochimica et biophysica acta. Gene regulatory mechanisms 10 32629174
2011 c-Jun N-terminal kinase activity supports multiple phases of 3D-mammary epithelial acinus formation. The International journal of developmental biology 10 22161830
2009 Cell-permeable Tat-NBD peptide attenuates rat pancreatitis and acinus cell inflammation response. World journal of gastroenterology 10 19195057
2014 The SAP motif and C-terminal RS- and RD/E-rich region influences the sub-nuclear localization of Acinus isoforms. Journal of cellular biochemistry 9 25079509
2013 Epstein-Barr virus latent membrane protein 2 effects on epithelial acinus development reveal distinct requirements for the PY and YEEA motifs. Journal of virology 9 24109232
1983 Differential filipin labeling of the luminal membranes lining the pancreatic acinus. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 9 6854007
2021 Engineering of a functional pancreatic acinus with reprogrammed cancer cells by induced PTF1a expression. Lab on a chip 8 34581719
2008 A novel role for acinus and MCM2 as host-specific signaling enhancers of DNA-damage-induced apoptosis in association with viral protein gp70. Leukemia research 8 19058849
1990 Streaming liver. VII: DNA turnover in acinus zone-3. Liver 8 2385154
2021 Prediction of hepatic drug clearance with a human microfluidic four-cell liver acinus microphysiology system. Toxicology 7 34543702
2021 Inhibition of cell proliferation and promotion of acinus-like structure formation from goat mammary epithelial cells via Wnt/β-catenin signaling. In vitro cellular & developmental biology. Animal 6 34312803
2020 Efficient Therapeutic Delivery by a Novel Cell-Penetrating Peptide Derived from Acinus. Cancers 6 32664285
2019 The arginine and serine-rich domains of Acinus modulate splicing. Cell biology international 6 31070279
2008 Gas diffusion in a pulmonary acinus model: experiments with hyperpolarized helium-3. Magnetic resonance imaging 6 18538524
1991 Homogeneous distribution of phosphofructokinase in the rat liver acinus: a quantitative histochemical study. Hepatology (Baltimore, Md.) 6 1833303
2025 Next-Generation Mapping of the ACINUS-Mediated Alternative Splicing Machinery and Its Regulation by O-glycosylation in Arabidopsis. bioRxiv : the preprint server for biology 4 40196518
2007 Spatial distribution of CYP2B1/2 messenger RNA within the rat liver acinus following exposure to the inducers phenobarbital and dieldrin. Toxicological sciences : an official journal of the Society of Toxicology 4 17517822
2006 AMPA-induced excitotoxicity increases nuclear levels of CAD, endonuclease G, and acinus and induces chromatin condensation in rat hippocampal pyramidal neurons. Cellular and molecular neurobiology 4 16767516
2025 The splicing factor Acin1 is essential for embryonic development but has limited effects on muscle structure and homeostasis. Scientific reports 3 40269054
2018 Crystal structure of human Acinus RNA recognition motif domain. PeerJ 3 30042883
1998 Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part XIII. A comparison of changes in the tracheobronchial epithelium and pulmonary acinus in male rats at 3 and 20 months. Research report (Health Effects Institute) 3 9697229
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2022 A phosphoswitch at acinus-serine437 controls autophagic responses to cadmium exposure and neurodegenerative stress. eLife 2 35037620
2019 Three-dimensional collective cell motions in an acinus-like lumen. Journal of biomechanics 2 30661732
2017 Using 3D Culture of Primary Mammary Epithelial Cells to Define Molecular Entities Required for Acinus Formation: Analyzing MAP Kinase Phosphatases. Methods in molecular biology (Clifton, N.J.) 2 27796954
2002 PCNA expression and electron microscopic study of acinus-forming hepatocytes in chronic hepatitis B. The Korean journal of internal medicine 2 12164086
1993 Occurrence of a third type of secretory cell in the acinus of the rat submandibular gland. The Anatomical record 2 7689795
2005 Temporal reduction in size of salivary acinus in rats induced by theophylline. Toxicologic pathology 1 15902964
2025 Recapitulation of clinical and molecular hallmarks of lipid-induced hepatic insulin resistance in a zonated, vascularized human liver acinus microphysiological system during metabolic dysfunction-associated steatotic liver disease (MASLD) progression. bioRxiv : the preprint server for biology 0 41279985
2022 Mathematical modeling of pulmonary acinus structure: Verification of acinar shape effects on pathway structure using rat lungs. Respiratory physiology & neurobiology 0 35367411
2015 Activated Acinus boosts basal autophagy. Molecular & cellular oncology 0 27308482
2011 [The expression of X-linked inhibitor of apoptosis protein and cell apoptosis in caerulein-stimulated rat pancreatic acinus AR42J cell lines]. Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 0 21604497
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