Affinage

ACIN1

Apoptotic chromatin condensation inducer in the nucleus · UniProt Q9UKV3

Length
1341 aa
Mass
151.9 kDa
Annotated
2026-06-09
98 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACIN1 (Acinus) is a dual-function nuclear protein that couples apoptotic chromatin dynamics to pre-mRNA splicing regulation (PMID:10490026, PMID:27365209). It was first identified as a caspase-3 substrate whose proteolytic cleavage generates an active p17 fragment that drives apoptotic nuclear changes (PMID:10490026); this activity is executed downstream by p17 binding to and activating PKC-delta, which promotes histone H2B phosphorylation, while ACIN1's principal apoptotic contribution is to internucleosomal DNA fragmentation rather than chromatin condensation per se (PMID:16537548, PMID:17721436). The pro-apoptotic activity is gated by phosphorylation: Akt directly phosphorylates ACIN1 at serine 422 and serine 573 to render it resistant to caspase cleavage (PMID:16177823), and this state is reinforced by partner proteins AAC-11 and zyxin that bind ACIN1 and protect it from cleavage (PMID:17572661, PMID:19387494). In its non-apoptotic role, ACIN1 is a peripheral exon junction complex component that binds pre-mRNA at suboptimal introns and regulates inclusion of weak alternative cassette exons, controlling splicing of targets including RARβ, Bcl-x, and the DNA-fragmentation regulator DFFA/ICAD (PMID:25205379, PMID:27365209). Its activity is shaped by kinase input—SRPK2 phosphorylation at S422 redistributes ACIN1 from nuclear speckles to nucleoplasm to upregulate cyclin A1 and drive cell-cycle progression (PMID:18559500), and ACIN1 is a direct mTORC1 substrate (PMID:25907765)—and by isoform-specific subnuclear targeting governed by its RS/RD-rich and SAP domains (PMID:25079509). In vivo, ACIN1 is essential for mouse embryonic development and for skeletal muscle homeostasis, where its loss alters splicing of muscle- and mitochondria-associated genes (PMID:40269054). Recurrent ACIN1-NUTM1 fusions retaining the ACIN1 SAP DNA-binding domain occur in infant acute lymphoblastic leukemia (PMID:31515871).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1999 High

    Established ACIN1 as a caspase-3-activated nuclear factor required for apoptotic nuclear morphology, defining its founding role in cell death.

    Evidence in vitro reconstitution with immunodepletion and antisense knockdown

    PMID:10490026

    Open questions at the time
    • Did not define the downstream effectors of the cleaved fragment
    • Relationship between chromatin condensation and DNA fragmentation left unresolved
  2. 2005 High

    Showed that Akt phosphorylation at S422/S573 shields ACIN1 from caspase cleavage, identifying a survival-signaling brake on its pro-apoptotic activation.

    Evidence in vitro kinase assay, phosphomimetic/phospho-dead mutagenesis, siRNA in apoptosis assays

    PMID:16177823

    Open questions at the time
    • Upstream signals controlling nuclear Akt activity not fully mapped
    • Did not address splicing functions of phosphorylated ACIN1
  3. 2006 High

    Reassigned ACIN1's apoptotic contribution from chromatin condensation to internucleosomal DNA fragmentation, refining the original 1999 model.

    Evidence inducible RNAi with intact-cell and cell-free apoptosis readouts

    PMID:16537548

    Open questions at the time
    • Mechanism linking ACIN1 to the DNA fragmentation machinery not defined here
    • Isoform-specific contributions not dissected
  4. 2007 High

    Identified the effector pathway of the ACIN1 p17 fragment—activation of PKC-delta leading to H2B phosphorylation—connecting cleavage to histone modification.

    Evidence reciprocal Co-IP, dominant-negative constructs, PKC-delta knockout MEFs, kinase assays

    PMID:17721436

    Open questions at the time
    • How H2B phosphorylation mechanically alters chromatin not resolved
    • Mst1 contribution remained ambiguous
  5. 2007 Medium

    Showed zyxin, recruited to the nucleus via Akt phosphorylation and 14-3-3γ, binds ACIN1-S and blocks its cleavage-dependent activity, adding a partner-mediated layer of apoptotic control.

    Evidence Co-IP, site-directed mutagenesis, nuclear fractionation, apoptosis assays

    PMID:17572661

    Open questions at the time
    • Single-lab finding without independent replication
    • Structural basis of zyxin-ACIN1 binding unknown
  6. 2008 High

    Revealed a cell-cycle role: SRPK2 phosphorylation at S422 relocalizes ACIN1 from speckles to nucleoplasm to upregulate cyclin A1, linking ACIN1 phospho-state to transcription and proliferation.

    Evidence Co-IP, in vitro kinase assay, phosphomutants, siRNA, cell-cycle analysis

    PMID:18559500

    Open questions at the time
    • Mechanism by which nucleoplasmic ACIN1 drives cyclin A1 transcription unclear
    • Whether speckle redistribution affects splicing not tested here
  7. 2009 High

    Identified AAC-11 as a leucine-zipper-dependent ACIN1 partner that protects against caspase cleavage, establishing a druggable anti-apoptotic interaction.

    Evidence Co-IP, in vitro caspase protection assay, siRNA, cell-permeable peptide competition

    PMID:19387494

    Open questions at the time
    • Whether AAC-11 affects ACIN1 splicing function not examined
    • In vivo relevance of the peptide not established
  8. 2009 Medium

    Linked ACIN1 to transcriptional corepression via Akt-promoted CtBP2 binding downstream of NGF/TrkA, opposing cyclin A1 expression.

    Evidence Co-IP, siRNA, luciferase reporter, kinase assay

    PMID:19668232

    Open questions at the time
    • Single-lab finding
    • Direct vs indirect effect on the cyclin A1 promoter not separated
  9. 2010 Medium

    Established a non-apoptotic role for the Drosophila ortholog in endosome stability and autophagosome maturation, broadening ACIN1 function into membrane trafficking and autophagy.

    Evidence loss-of-function genetic screen, genetic interactions, trafficking and autophagy assays in Drosophila

    PMID:20504956

    Open questions at the time
    • Conservation of trafficking role in mammals untested
    • Molecular mechanism of endosome stabilization unknown
  10. 2014 Medium

    Defined isoform-specific subnuclear targeting of ACIN1, mapping speckle localization to the RS/RD-rich region and nucleoplasmic localization to the SAP-containing N-terminus.

    Evidence fluorescence microscopy with domain deletion constructs and SC35 co-localization

    PMID:25079509

    Open questions at the time
    • Functional consequence of cross-isoform localization influence unclear
    • Single-lab finding
  11. 2014 Medium

    Demonstrated in Drosophila that caspase cleavage and Akt phosphorylation control Acinus stability to set basal autophagy, with stabilized forms conferring neuroprotection and longevity.

    Evidence caspase loss-of-function, phosphomimetic/cleavage-resistant mutants, autophagy flux, neurodegeneration and lifespan assays

    PMID:25332163

    Open questions at the time
    • Mammalian relevance of the autophagy-stability axis untested
    • Molecular link from Acinus to autophagosome formation undefined
  12. 2015 Medium

    Established ACIN1 as a sequence-context splicing enhancer of weak cassette exons, with the RRM required for retinoic-acid-dependent activity and RNPS1 repressing RA-independent activity.

    Evidence minigene splicing assays, domain deletion mutagenesis, endogenous RARβ/Bcl-x readouts

    PMID:25205379

    Open questions at the time
    • Genome-wide target scope not addressed here
    • Mechanism of RNPS1 repression unclear
  13. 2015 Medium

    Identified ACIN1-L as a direct, nutrient-responsive mTORC1 substrate, placing it under growth-signaling control.

    Evidence quantitative phosphoproteomics, mTOR interactomics, Co-IP, MS-enhanced kinase assay

    PMID:25907765

    Open questions at the time
    • Functional consequence of mTORC1 phosphorylation on splicing or apoptosis not defined
    • Single-lab finding
  14. 2016 High

    Provided a genome-wide binding and functional map confirming ACIN1 as a peripheral EJC component that binds suboptimal introns and directly regulates splicing of DFFA/ICAD, unifying its splicing and apoptosis roles.

    Evidence iCLIP, siRNA depletion, RNA-seq in HeLa cells

    PMID:27365209

    Open questions at the time
    • Causal link between ICAD splicing changes and apoptotic outcome not directly tested
    • Determinants of suboptimal-intron selectivity unresolved
  15. 2017 High

    Showed Cdk5/p35 phosphorylation of conserved S437 stabilizes Acinus and drives starvation-independent basal autophagy with selective neuroprotection in Drosophila.

    Evidence Cdk5/p35 gain- and loss-of-function, phospho-specific antibody, phosphomimetic rescue in neurodegeneration models

    PMID:29227247

    Open questions at the time
    • Why protection is restricted to certain aggregating proteins not explained
    • Mammalian ACIN1 S437 equivalent not validated
  16. 2018 Medium

    Solved the human ACIN1 RRM crystal structure, revealing a C-terminal helix that occludes the RNA-binding surface and harbors the caspase-3 cleavage site, suggesting cleavage unmasks RNA binding.

    Evidence X-ray crystallography at 1.65 Å

    PMID:30042883

    Open questions at the time
    • Occlusion model not functionally validated in the study
    • No structure of full-length or RNA-bound ACIN1
  17. 2018 Medium

    Identified the PPM-type phosphatase Nil as the counteracting enzyme controlling pS437-Acn levels, defining bidirectional phospho-regulation of autophagy.

    Evidence genetic phosphatase screen, loss-of-function mutants, phospho-specific antibody, autophagy/neurodegeneration assays

    PMID:29782227

    Open questions at the time
    • Mammalian phosphatase counterpart unknown
    • Single-lab finding
  18. 2019 Medium

    Discovered recurrent ACIN1-NUTM1 fusions retaining the ACIN1 SAP domain in infant ALL, implicating ACIN1 in oncogenic rearrangement.

    Evidence transcriptome sequencing with RT-PCR confirmation and cytogenetics

    PMID:31515871

    Open questions at the time
    • No functional characterization of the fusion protein
    • Mechanism of leukemogenesis untested
  19. 2019 Low

    Mapped RS and RSB domains as modulators of splice-site selection in a tethered reporter, providing low-resolution domain dissection of ACIN1 splicing activity.

    Evidence tethered minigene reporter splicing assay

    PMID:31070279

    Open questions at the time
    • Single method, single lab without orthogonal validation
    • Full-length ACIN1-S' showed no effect, leaving physiological relevance unclear
  20. 2020 Medium

    Showed an SRSF3/MBNL1-driven splicing switch shifts Acin1 from the S to the L isoform to suppress DNA fragmentation under oxidative stress in cancer cells, tying isoform choice to apoptotic resistance.

    Evidence whole-transcriptome analysis, minigene assay, siRNA, DNA fragmentation assay

    PMID:33142236

    Open questions at the time
    • Direct molecular basis of isoform-specific fragmentation difference unresolved
    • Single-lab finding
  21. 2020 Medium

    Demonstrated isoform-specific ACIN1 control of brown adipogenesis through SRSF3 splicing-coupled NMD, extending its splicing regulation to cell differentiation.

    Evidence siRNA, isoform overexpression, RNA-seq, differentiation assays in fibroblasts

    PMID:32629174

    Open questions at the time
    • Relevance to in vivo adipose biology untested
    • Single-lab finding
  22. 2022 Medium

    Established that the Nil phosphatase counterbalances Cdk5 at Acn-S437 and that environmental Cd2+ tunes this axis to control neuronal autophagy and survival.

    Evidence genetic phosphatase screen, loss-of-function, phospho-specific antibody, cadmium exposure, autophagy/viability assays

    PMID:35037620

    Open questions at the time
    • Mammalian conservation of the Cd2+-responsive axis untested
    • Direct phosphatase-substrate biochemistry not reconstituted
  23. 2025 Medium

    Showed ACIN1 is essential in vivo, with global knockout causing embryonic lethality and muscle-specific loss disrupting splicing of muscle and mitochondrial genes, establishing a developmental and tissue-homeostatic requirement.

    Evidence conditional and global knockout mice, RNA-seq, immunohistochemistry

    PMID:40269054

    Open questions at the time
    • Causal mis-spliced targets driving the muscle phenotype not isolated
    • Embryonic lethality mechanism undefined
  24. 2025 Low

    Implicated ACIN1 as an SRRM2 interaction partner in the nuclear speckle/splicing machinery, with an ALS-associated SRRM2 mutation disrupting the interaction.

    Evidence endogenous point-mutation cell line and protein-protein interaction assay (preprint)

    Open questions at the time
    • Preprint without peer review and no mechanistic follow-up on ACIN1
    • Functional consequence for ACIN1 splicing activity unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the apoptotic, splicing, cell-cycle, and autophagy functions of ACIN1 are integrated in a single mammalian cell—and which mis-spliced targets mediate its developmental essentiality—remains unresolved.
  • No unified model linking phospho-state, isoform, and localization to specific cellular outcomes
  • Mammalian autophagy role of ACIN1 not directly demonstrated
  • Functional consequences of the ACIN1-NUTM1 fusion uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0140110 transcription regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 3 R-HSA-8953854 Metabolism of RNA 2
Partners
AAC-11AKT1CTBP2PRKCDRNPS1SRPK2SRRM2ZYX
Complex memberships
ASAP/PSAP complex (with RNPS1, SAP18)exon junction complex (EJC)

Evidence

Reading pass · 24 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 showed Acinus is essential for apoptotic chromatin condensation in vitro. In vitro reconstitution system, immunodepletion, antisense knockdown Nature High 10490026
2005 Akt directly phosphorylates Acinus on serine 422 and serine 573, making Acinus resistant to caspase cleavage in the nucleus and inhibiting Acinus-dependent chromatin condensation. Phosphomimetic mutant (S422,573D) resists apoptotic cleavage; unphosphorylatable mutant accelerates chromatin condensation. Nuclear Akt depletion provokes apoptotic cleavage of Acinus. In vitro kinase assay, site-directed mutagenesis, siRNA knockdown, cell-based apoptosis assays The EMBO journal High 16177823
2006 Knockdown of Acinus isoforms by inducible RNAi does not inhibit apoptotic chromatin condensation but does reduce oligonucleosomal DNA fragmentation, indicating Acinus contributes to internucleosomal DNA cleavage rather than chromatin condensation during apoptosis. Acinus is not required for nuclear localization of ASAP complex subunits SAP18 and RNPS1. Inducible RNAi stable knockdown, cell-free apoptosis system, DNA fragmentation assay The Journal of biological chemistry High 16537548
2007 The caspase-cleaved active Acinus p17 fragment promotes apoptotic chromatin condensation by binding to both Mst1 and PKC-delta, enhancing their kinase activities, leading to histone H2B phosphorylation. Dominant-negative PKC-delta (but not Mst1) blocks Acinus-initiated H2B phosphorylation. PKC-delta-deficient MEFs and siRNA-depleted PC12 cells abolish acinus-elicited H2B phosphorylation and chromatin condensation. Co-immunoprecipitation, dominant-negative constructs, siRNA knockdown, PKC-delta knockout MEFs, kinase activity assays Cell death and differentiation High 17721436
2007 Akt phosphorylates zyxin on serine 142, leading to zyxin's association with Acinus-S in the nucleus and prevention of Acinus-S-triggered chromatin condensation. 14-3-3γ (but not ζ) selectively triggers zyxin nuclear translocation in an Akt-phosphorylation-dependent manner. The zyxin S142D phosphomimetic mutant diminishes Acinus proteolytic cleavage and chromatin condensation. Co-immunoprecipitation, site-directed mutagenesis, nuclear fractionation, apoptosis assays Cell death and differentiation Medium 17572661
2008 SRPK2 binds and phosphorylates Acinus, redistributing it from nuclear speckles to the nucleoplasm, resulting in cyclin A1 (but not A2) upregulation. Acinus S422D (SRPK2 phosphorylation mimetic) enhances cyclin A1 transcription; S422A blocks SRPK2's stimulatory effect. Ablation of Acinus or SRPK2 abrogates cyclin A1 expression and arrests leukemia cells at G1. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, siRNA knockdown, cell cycle analysis Cancer research High 18559500
2009 AAC-11 physically interacts with Acinus via its leucine-zipper domain and protects Acinus from caspase-3 cleavage in vivo and in vitro, thereby preventing Acinus-mediated DNA fragmentation. A cell-permeable peptide mimicking the leucine-zipper subdomain of AAC-11 disrupts AAC-11–Acinus complex formation and potentiates drug-mediated apoptosis. Co-immunoprecipitation, in vitro caspase cleavage assay, siRNA knockdown, cell-permeable peptide competition The EMBO journal High 19387494
2009 Transcription corepressor CtBP2 directly binds Acinus, and this interaction is promoted by Akt-mediated phosphorylation of Acinus triggered by NGF/TrkA signaling. CtBP2 overexpression diminishes cyclin A1 transcription; CtBP2 depletion abolishes NGF's suppressive effect on cyclin A1 expression. Co-immunoprecipitation, siRNA knockdown, luciferase reporter assay, kinase assay Oncogene Medium 19668232
2010 Drosophila Acinus (dacn) is required for stabilization of early endosomes, modulating Notch and Egfr signaling levels. Loss of dacn also inhibits autophagosome maturation in response to starvation, while dacn overexpression causes lethality through enhanced autophagy independent of the Tor pathway. Loss-of-function genetic screen, genetic interaction, endosomal trafficking assays, autophagy assays Development (Cambridge, England) Medium 20504956
2014 In Drosophila, Acinus (Acn) stability and basal autophagy regulation depend on proteolytic cleavage by the caspase Dcp-1 and on AKT1-mediated phosphorylation. Flies expressing stabilized Acn forms (phosphomimetic S641,731D or caspase-resistant D527A) exhibit enhanced basal autophagy, increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged lifespan. Caspase loss-of-function, site-directed mutagenesis, autophagy flux assays, in vivo neurodegeneration models, lifespan analysis The Journal of cell biology Medium 25332163
2015 Acinus L is a direct substrate of mTORC1; it was identified by overlapping quantitative phosphoproteomics (upon raptor inhibition) with endogenous mTOR interactomics, and confirmed by co-immunoprecipitation and MS-enhanced kinase assays showing insulin- and amino-acid-responsive phosphorylation. Quantitative phosphoproteomics, co-immunoprecipitation, MS-enhanced in vitro kinase assay Molecular & cellular proteomics : MCP Medium 25907765
2015 Acinus functions in pre-mRNA splicing by enhancing inclusion of weak alternative cassette exons in a retinoic acid (RA)-dependent and -independent manner. The RRM domain is necessary for RA-dependent splicing activity, and RNPS1 represses the RA-independent splicing activity of Acinus. Acinus stimulates alternative 5' splice site usage of endogenous RARβ and Bcl-x transcripts. In vivo minigene splicing assays, domain deletion mutagenesis, endogenous pre-mRNA splicing assays Journal of cellular physiology Medium 25205379
2016 iCLIP mapping shows Acinus binds pre-mRNAs at a subset of suboptimal introns and also associates with spliced mRNAs, confirming its role as a peripheral EJC component. siRNA depletion of Acinus in HeLa cells preferentially disrupts inclusion of specific alternative cassette exons and faithful splicing of a subset of introns. Acinus directly regulates splicing of DFFA/ICAD transcript, a major DNA fragmentation regulator. iCLIP (cross-linking immunoprecipitation), siRNA depletion, RNA-seq RNA (New York, N.Y.) High 27365209
2017 In Drosophila, Cdk5 phosphorylates Acinus at serine 437 to stabilize it and promote starvation-independent basal autophagy. Loss of Cdk5 or its cofactor p35 reduces pS437-Acn levels and basal autophagy. The phosphomimetic S437D mutation stabilizes Acn and promotes basal autophagy, and rescues neurodegeneration induced by polyQ proteins and Aβ42 (but not alpha-Synuclein). Genetic gain- and loss-of-function (Cdk5, p35 mutants), site-directed mutagenesis, autophagy assays, in vivo neurodegeneration models eLife High 29227247
2018 The crystal structure of the human Acinus RRM domain was solved at 1.65 Å resolution, revealing a classical four-stranded antiparallel β-sheet with two flanking α-helices plus an additional C-terminal α-helix. The C-terminal helix partially occludes the ligand-binding surface of the β-sheet and harbors the caspase-3 target cleavage sequence, suggesting it shields RNA binding until proteolytic activation. X-ray crystallography PeerJ Medium 30042883
2014 The sub-nuclear localization of Acinus isoforms differs: Acinus-S' colocalizes with SC35 in nuclear speckles (dependent on its C-terminal RS- and RD/E-rich region), while Acinus-L localizes diffusely in the nucleoplasm (dependent on its unique N-terminal SAP motif). The two isoforms influence each other's localization when co-expressed. Fluorescence microscopy, domain deletion/mutation constructs, co-localization with SC35 marker Journal of cellular biochemistry Medium 25079509
2018 Cdk5-mediated phosphorylation of Acn-S437 (Drosophila Acinus) is identified as a key regulator of basal autophagy, independent of metabolic stress. In nil1 (PPM-type phosphatase) loss-of-function animals, pS437-Acn levels are elevated, increasing neuronal autophagy and reducing polyQ accumulation in a Huntington's disease model. Genetic phosphatase screen, loss-of-function mutants, phospho-specific antibody, autophagy and neurodegeneration assays Autophagy Medium 29782227
2019 Recurrent ACIN1-NUTM1 gene fusions (joining exons 3 or 4 of ACIN1 to exon 3 of NUTM1) were identified in non-KMT2A-rearranged infant ALL by transcriptome analysis. The fusion transcripts contain the functional SAP (SAF-A/B, Acinus, and PIAS) DNA-binding domain of ACIN1 and most of NUTM1. Transcriptome sequencing (RNA-seq), RT-PCR confirmation, cytogenetic analysis Genes, chromosomes & cancer Medium 31515871
2019 The RS (arginine/serine-rich) and RSB (RNPS1-SAP18-binding) domains of Acinus can modulate alternative splice site selection when tethered in an HIV-1 minigene reporter system, while full-length Acinus-S' does not affect splice site selection in this system. In vivo splicing assay with tethering constructs, minigene reporter Cell biology international Low 31070279
2020 Elevated SRSF3 promotes inclusion of MBNL1 exons 5 and 7 via CA-rich exonic elements, and an increase in the resulting MBNL18 isoform shifts Acin1 splicing from the Acin1-S to the Acin1-L isoform, leading to diminished DNA fragmentation under oxidative stress in colorectal cancer cells. Whole-transcriptome analysis, minigene splicing assay, siRNA knockdown, DNA fragmentation assay Neoplasia (New York, N.Y.) Medium 33142236
2020 Depletion of endogenous Acin1 isoforms activates brown adipogenic signatures in mouse C3H10T1/2 fibroblasts. Overexpression of Acin1-L versus Acin1-S exerts discriminative influences on brown adipogenesis through modulation of SRSF3 expression via an alternative splicing-coupled nonsense-mediated decay mechanism in a sequence-specific manner. siRNA knockdown, isoform overexpression, RNA-seq, splicing assays, brown adipogenesis differentiation assays Biochimica et biophysica acta. Gene regulatory mechanisms Medium 32629174
2022 The PPM-type phosphatase Nil (CG6036) counterbalances Cdk5-dependent phosphorylation of Acinus-S437 in Drosophila neurons. Loss of Nil enhances pS437-Acn levels and elevates neuronal autophagy. Cd2+ exposure inhibits this PPM-type phosphatase, elevating acn-S437 phosphorylation, which is required for increased neuronal autophagy and protection against Cd2+-induced cytotoxicity. Genetic phosphatase screen, loss-of-function mutants, phospho-specific antibody, cadmium exposure, autophagy and viability assays eLife Medium 35037620
2025 Global deletion of Acin1 in mice causes embryonic lethality around E11.5, with developmental delays and increased apoptosis. Skeletal muscle myofiber-specific Acin1 knockout mice show enlarged myofibers, muscle damage, and regeneration. RNA-seq reveals that Acin1 deletion alters expression and splicing of genes crucial for muscle function, including splicing changes in genes associated with muscle disease and mitochondrial function, often producing immature or disease-associated splice variants. Conditional and global knockout mice, RNA-seq, immunohistochemistry, central nuclei counting Scientific reports Medium 40269054
2025 A point mutation in SRRM2 associated with ALS disrupts the protein-protein interaction between SRRM2 and the splicing factor ACIN1, revealing ACIN1 as a binding partner of SRRM2 in the nuclear speckle/splicing machinery. Endogenous gene point mutation in cell line, protein-protein interaction assay bioRxivpreprint Low

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 362 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 138 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 108 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 75 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
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
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.) 38 27365209
1994 Endothelial cell heterogeneity in the normal human liver acinus: in situ immunohistochemical demonstration. Liver 38 8078390
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 34 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
2019 Cryptic recurrent ACIN1-NUTM1 fusions in non-KMT2A-rearranged infant acute lymphoblastic leukemia. Genes, chromosomes & cancer 29 31515871
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
2019 Mechanical Stabilization of the Glandular Acinus by Linker of Nucleoskeleton and Cytoskeleton Complex. Current biology : CB 28 31402305
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
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
2013 A microfluidic device mimicking acinar concentration gradients across the liver acinus. Biomedical microdevices 22 23563756
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
2022 Liver Acinus Dynamic Chip for Assessment of Drug-Induced Zonal Hepatotoxicity. Biosensors 19 35884248
2018 Measuring Hypopharyngeal Gland Acinus Size in Honey Bee (Apis mellifera) Workers. Journal of visualized experiments : JoVE 19 30272666
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 18 25907765
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
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
2006 Small Rho GTPases are important for acinus formation in a human salivary gland cell line. Cell and tissue research 13 16639616
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
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
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 11 32629174
2018 Cdk5-mediated Acn/Acinus phosphorylation regulates basal autophagy independently of metabolic stress. Autophagy 11 29782227
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
2021 Engineering of a functional pancreatic acinus with reprogrammed cancer cells by induced PTF1a expression. Lab on a chip 9 34581719
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
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
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
1995 Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part IX: Changes in the tracheobronchial epithelium, pulmonary acinus, and lung antioxidant enzyme activity. Research report (Health Effects Institute) 3 7619334
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
2022 Mathematical modeling of pulmonary acinus structure: Verification of acinar shape effects on pathway structure using rat lungs. Respiratory physiology & neurobiology 1 35367411
2005 Temporal reduction in size of salivary acinus in rats induced by theophylline. Toxicologic pathology 1 15902964
2026 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. BMC biotechnology 0 42063103
2026 Scaling human liver microphysiological systems: implementing a higher-throughput liver acinus microphysiological system platform. Experimental biology and medicine (Maywood, N.J.) 0 42255464
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
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
2002 [Detection of hepatoid glands and distinctive features of hepatoid acinus]. Izvestiia Akademii nauk. Seriia biologicheskaia 0 12561331
1986 Microcorrosion casting of the human respiratory acinus. Scanning electron microscopy 0 3798013

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