Affinage

ASPM

Abnormal spindle-like microcephaly-associated protein · UniProt Q8IZT6

Length
3477 aa
Mass
409.8 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASPM is a microtubule minus-end-associated protein that focuses spindle poles, regulates DNA damage responses, and co-activates Wnt/β-catenin signaling, with loss-of-function mutations causing autosomal recessive primary microcephaly. At spindle poles, ASPM autonomously tracks growing microtubule minus ends, cross-links microtubule bundles to focus poles, and forms a complex with the katanin p60/p80 severing enzyme—resolved by crystallography—to regulate spindle flux and microtubule disassembly; it acts redundantly with CDK5RAP2 in pole focusing and requires Polo kinase phosphorylation for centrosomal aster nucleation (PMID:26644514, PMID:28436967, PMID:28883092, PMID:11283617). Beyond the spindle, ASPM is recruited to DNA double-strand breaks in a PARP2-dependent manner where it stabilizes BRCA1 by blocking HERC2-mediated ubiquitination, and it localizes to stalled replication forks via RAD17 to promote RAD9/TopBP1 loading and ATR-CHK1 checkpoint activation (PMID:34142045, PMID:36161901). In neural progenitors, ASPM modulates Cyclin E ubiquitination and Cdk2/Cyclin E-dependent G1 progression, and stabilizes Dishevelled-3 against proteasomal degradation to potentiate canonical Wnt/β-catenin transcriptional activity, thereby maintaining the proliferative symmetric division mode required for cortical expansion (PMID:26581405, PMID:21937711, PMID:30266990).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    The fundamental cellular role of ASPM at spindle poles was established: Drosophila Asp localizes to poles independently of centrosomes and is required for microtubule focusing into bipolar spindles and for central spindle organization, resolving whether this protein acts in microtubule nucleation versus pole organization.

    Evidence Genetic mutant analysis, immunofluorescence, epistasis with asterless, and colchicine treatment in Drosophila

    PMID:11352927

    Open questions at the time
    • Mechanism of microtubule focusing by Asp (cross-linking vs. anchoring) not resolved
    • Whether vertebrate ASPM performs the identical function was untested
    • Regulation of Asp localization unknown
  2. 2001 High

    A regulatory input to ASPM was identified: Polo kinase phosphorylates Asp, and this phosphorylation is required together with γ-tubulin to reconstitute microtubule aster nucleation from stripped centrosomes, establishing a direct kinase-substrate relationship governing centrosome function.

    Evidence In vitro kinase assay, reciprocal co-immunoprecipitation, sucrose gradient sedimentation, and centrosome reconstitution assay in Drosophila embryo extracts

    PMID:11283617

    Open questions at the time
    • Phosphorylation sites on Asp not mapped
    • Whether Polo regulation is conserved in mammalian ASPM unknown
    • How phosphorylation alters Asp biochemical activity not defined
  3. 2005 Medium

    Human ASPM was shown to localize to centrosomes/spindle poles throughout the cell cycle, and its depletion reduced BRCA1 protein levels, first linking ASPM to genome integrity pathways beyond spindle function.

    Evidence siRNA knockdown, immunofluorescence, and Western blot in human cells

    PMID:16123590

    Open questions at the time
    • Mechanism by which ASPM stabilizes BRCA1 not identified
    • Whether BRCA1 reduction is a direct or indirect effect unknown
    • Functional consequence on DNA repair not tested
  4. 2007 Medium

    Domain mapping of ASPM revealed that its C-terminus mediates spindle pole and midbody localization and that all microcephaly-causing mutations truncate this region, connecting patient genetics to a specific protein domain; ASPM also interacts with citron kinase at the midbody, implicating it in cytokinesis.

    Evidence GFP-fragment localization, co-immunoprecipitation with citron kinase in HeLa and embryonic neuroepithelium

    PMID:17534152

    Open questions at the time
    • Functional significance of the ASPM-citron kinase interaction not demonstrated by loss-of-function
    • Whether midbody function is separable from pole function untested
  5. 2010 High

    ASPM was established as a bona fide microtubule minus-end protein whose C-terminal domain is essential for spindle pole recruitment; a patient splice-site mutation disrupting this domain abolished pole localization and caused spindle/cytokinesis defects, directly linking the molecular defect to disease pathology.

    Evidence siRNA knockdown, live-cell imaging, patient fibroblast analysis, dominant-negative expression in U2OS cells

    PMID:21044324

    Open questions at the time
    • Structural basis for minus-end recognition not resolved
    • Whether the dominant-negative effect reflects physiological stoichiometry not assessed
  6. 2011 High

    A non-mitotic role for ASPM emerged: it positively regulates Wnt/β-catenin signaling in the developing brain, and constitutively active β-catenin rescues cortical defects caused by Aspm knockdown, establishing that ASPM-dependent microcephaly involves defective Wnt-driven progenitor proliferation.

    Evidence In utero electroporation knockdown in mouse cortex, Wnt luciferase reporter, stabilized β-catenin rescue

    PMID:21937711

    Open questions at the time
    • Direct binding partner in Wnt pathway not yet identified
    • Whether Wnt role is separable from spindle pole role unclear
  7. 2011 Medium

    ASPM was shown to participate in DNA double-strand break repair, acting in a DNA-PK-dependent (NHEJ) pathway, broadening its known functions to genome maintenance.

    Evidence siRNA knockdown, constant-field gel electrophoresis, γ-H2AX foci, epistasis with DNA-PK-deficient cells

    PMID:21923303

    Open questions at the time
    • Mechanism of ASPM action in NHEJ not defined
    • Whether ASPM also contributes to HR not addressed
    • No structural or biochemical basis provided
  8. 2014 High

    The conserved functional partnership between ASPM and katanin was demonstrated: C. elegans ASPM-1 and the katanin MEI-1 are jointly required for meiotic spindle pole assembly, with katanin recruiting ASPM-1 to spindles, establishing evolutionary conservation of the ASPM-katanin axis.

    Evidence Temperature-sensitive alleles, live-cell imaging, and genetic epistasis in C. elegans oocyte meiosis

    PMID:24554763

    Open questions at the time
    • Biochemical basis of ASPM-1–MEI-1 interaction not resolved
    • Whether mammalian ASPM-katanin interaction operates identically in meiosis untested
  9. 2015 High

    The biochemical mechanism of pole focusing was resolved: Drosophila Asp cross-links microtubule minus ends via a defined domain and focuses augmin-nucleated intraspindle microtubules during flux, independent of Ncd motor activity.

    Evidence In vitro microtubule cross-linking assay, RNAi depletion, live-cell imaging, domain analysis in Drosophila S2 cells

    PMID:26644514

    Open questions at the time
    • Whether human ASPM has identical cross-linking activity in vitro not shown
    • Structural basis of the cross-linking domain not determined
  10. 2015 High

    ASPM was linked to G1 cell cycle control: it interacts with Cdk2/Cyclin E, modulates Cyclin E ubiquitination and nuclear translocation, and its mutation in mice leads to premature neural progenitor exhaustion due to shortened pre-restriction-point G1.

    Evidence ASPM knock-in mouse model, co-immunoprecipitation, ubiquitination assay, cell cycle analysis

    PMID:26581405

    Open questions at the time
    • Whether ASPM directly inhibits the E3 ligase for Cyclin E or acts indirectly unclear
    • Relationship between Cyclin E regulation and Wnt signaling by ASPM not integrated
  11. 2017 High

    The molecular interface between ASPM and katanin was solved at atomic resolution, and reconstitution demonstrated that ASPM autonomously tracks growing microtubule minus ends, inhibits their growth, and cooperates with katanin to promote severing and regulate spindle flux—providing the most detailed mechanistic picture of ASPM's spindle function.

    Evidence X-ray crystallography of ASPM-katanin interface, TIRF-based in vitro reconstitution of minus-end tracking and severing, co-immunoprecipitation, siRNA in human cells

    PMID:28436967

    Open questions at the time
    • Full-length ASPM structure unavailable
    • How disease-associated truncations alter the ASPM-katanin complex biochemically not tested in vitro
    • Regulation of the ASPM-katanin interaction during the cell cycle unknown
  12. 2017 High

    Genetic redundancy with CDK5RAP2 was revealed: ASPM knockout alone does not disrupt spindle morphology in human cells, but combined loss with CDK5RAP2 causes severe pole unfocusing, explaining the mild spindle phenotype in ASPM-null cells and highlighting compensatory mechanisms.

    Evidence CRISPR knockout, auxin-inducible degron depletion, siRNA, live-cell imaging in human cells

    PMID:28883092

    Open questions at the time
    • Whether additional redundant factors exist is unknown
    • How CDK5RAP2 compensates mechanistically (independent minus-end focusing?) not resolved
  13. 2018 High

    The molecular basis for ASPM's Wnt co-activation was identified: ASPM binds Dishevelled-3 and prevents its proteasomal degradation, stabilizing Dvl-3 to enable β-catenin-dependent transcription, directly linking the earlier in vivo Wnt rescue finding to a specific protein interaction.

    Evidence Reciprocal co-immunoprecipitation, proteasome inhibitor rescue, siRNA knockdown, tumorigenicity assay in prostate cancer cells

    PMID:30266990

    Open questions at the time
    • Whether ASPM also stabilizes Dvl-2 or other Dvl isoforms not tested
    • Structural basis of ASPM-Dvl-3 interaction unknown
    • Whether this mechanism operates in neural progenitors in vivo not confirmed
  14. 2021 High

    The mechanism of ASPM's BRCA1-stabilizing role in DNA repair was resolved: ASPM is recruited to DSBs in a PARP2-dependent manner and blocks HERC2-mediated ubiquitination and degradation of BRCA1, thereby enabling homologous recombination; this also reconciled the earlier finding on HR rather than NHEJ as the primary repair pathway affected.

    Evidence Co-immunoprecipitation, PARP2 knockdown, HERC2 ubiquitination assay, HR reporter assay, irradiation sensitivity in human cells

    PMID:34142045

    Open questions at the time
    • Whether ASPM also promotes NHEJ as earlier suggested, or whether those findings reflected indirect effects via BRCA1, remains unclear
    • ASPM's role at DSBs versus replication forks not yet integrated
  15. 2022 High

    ASPM was found at stalled replication forks via RAD17-dependent recruitment, where it promotes RAD9/TopBP1 chromatin loading and ATR-CHK1 checkpoint activation; its loss causes fork degradation and chromosomal instability, establishing a replication stress checkpoint function distinct from its DSB repair role.

    Evidence iPOND, chromatin fractionation, ATR-CHK1 phosphorylation assay, DNA fiber assay, siRNA knockdown in human cells

    PMID:36161901

    Open questions at the time
    • How ASPM structurally engages the 9-1-1 clamp loader complex unknown
    • Whether replication fork function contributes to microcephaly pathology not tested
    • Whether the spindle and DNA damage roles are coordinated across the cell cycle is unclear
  16. 2024 Medium

    Isoform-specific regulation of ASPM's Wnt function was uncovered: alternative splicing controlled by RBM10/SRSF2 determines inclusion of exon 18, generating an ASPM isoform that stabilizes DVL2 and enhances β-catenin signaling, revealing that splicing regulation diversifies ASPM's signaling output.

    Evidence Minigene splicing reporter, co-immunoprecipitation, RNA sequencing, functional assays in cholangiocarcinoma cells

    PMID:38576051

    Open questions at the time
    • Whether exon 18-containing isoform differs in spindle function unknown
    • DVL2 versus DVL3 stabilization by different isoforms not systematically compared
    • In vivo relevance of isoform switching in brain development not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how ASPM's spindle pole, Wnt signaling, and DNA damage/replication stress functions are coordinately regulated across the cell cycle; which functions are most critical for microcephaly pathogenesis; and what the full-length structure of ASPM looks like, particularly how disease-associated truncations alter its multiple interaction interfaces.
  • No full-length structure of mammalian ASPM
  • Relative contributions of spindle, Wnt, and DNA damage functions to microcephaly not dissected in vivo
  • Cell-cycle-dependent regulation of ASPM's partitioning between chromatin and spindle unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005815 microtubule organizing center 7 GO:0005856 cytoskeleton 5 GO:0005694 chromosome 2
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-162582 Signal Transduction 4 R-HSA-73894 DNA Repair 3 R-HSA-1266738 Developmental Biology 2
Partners
BRCA1CCNE1CDK5RAP2CITKDVL3HERC2KATNA1KATNB1
Complex memberships
ASPM-katanin complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Drosophila Asp (ASPM ortholog) is a 220-kDa microtubule-associated protein that localizes to spindle poles independently of functional centrosomes; in asp mutants, microtubule nucleation occurs normally but spindle pole focusing and central spindle organization are severely defective, leading to cytokinesis failure. Asp is required for aggregation of microtubules into focused spindle poles and for formation of the central spindle. Genetic mutant analysis (asp mutants), immunofluorescence, double mutant epistasis with asterless, colchicine treatment The Journal of cell biology High 11352927
2001 Drosophila Asp is a substrate of Polo kinase; Polo phosphorylates Asp in vitro, generating an MPM2 epitope. Polo and Asp co-immunoprecipitate and exist in a 25–38S complex. Phosphorylated Asp is required (together with gamma-tubulin) to restore microtubule aster nucleation in salt-stripped centrosomes, and extracts from polo mutant embryos fail this rescue unless supplemented with phosphorylated Asp or active Polo kinase. In vitro kinase assay, co-immunoprecipitation, sucrose gradient sedimentation, centrosome reconstitution assay Nature cell biology High 11283617
2005 Human ASPM localizes to the centrosome during interphase and to spindle poles from prophase through telophase; siRNA-mediated downregulation of ASPM decreases endogenous BRCA1 protein levels, suggesting ASPM regulates BRCA1 at the centrosome/spindle pole. siRNA knockdown, immunofluorescence, Western blot Cell cycle (Georgetown, Tex.) Medium 16123590
2005 RNAi depletion of Drosophila Asp in S2 cells produces severe loss of spindle pole focus; Asp localizes to focused poles and is subtly mislocalized after dynein-dynactin depletion, indicating complex interdependence between dynein-dynactin, Asp, and KLP10A in spindle pole focusing and centrosome attachment. RNAi depletion, immunofluorescence, quantitative spindle analysis Molecular biology of the cell Medium 15888542
2007 Human ASPM co-localizes with citron kinase (CITK) at the midbody ring during cytokinesis and co-immunoprecipitates with CITK from HeLa cell lysates and embryonic neuroepithelium. The N-terminal fragment of ASPM localizes to centrosomes/spindle poles, while the C-terminal fragment localizes to midbodies; all microcephaly-causing ASPM mutations truncate the C-terminus. Co-immunoprecipitation, GFP-fragment localization, immunofluorescence Cell cycle (Georgetown, Tex.) Medium 17534152
2010 Human ASPM is a microtubule minus-end-associated protein recruited in a microtubule-dependent manner to the pericentriolar matrix at spindle poles. siRNA depletion perturbs spindle orientation and causes cytokinesis failure in U2OS cells. A pathogenic splice-site mutation causing loss of a tripeptide from the C-terminus dramatically reduces ASPM spindle pole localization. Dominant-negative C-terminal ASPM fragments cause spindle assembly defects and cytokinesis failure. siRNA knockdown, immunofluorescence, live-cell imaging, patient fibroblast analysis, dominant-negative expression BMC cell biology High 21044324
2011 ASPM regulates Wnt signaling during brain development: Aspm knockdown in the developing mouse brain reduces Wnt-mediated transcription, and expression of stabilized β-catenin rescues both the signaling deficit and the in vivo cortical defects caused by Aspm knockdown. In utero electroporation knockdown, luciferase reporter assay, β-catenin rescue experiment Genes & development High 21937711
2012 ASPM localizes to the entire spindle during mouse oocyte meiosis and co-localizes with acetylated tubulin. Morpholino-mediated knockdown causes elongated meiotic spindles and arrest at metaphase I. ASPM co-immunoprecipitates with calmodulin in metaphase I oocytes, and the two proteins co-localize at the spindle. Morpholino knockdown, immunofluorescence, co-immunoprecipitation, mass spectrometry PloS one Medium 23152892
2014 In C. elegans, the calponin homology domain protein ASPM-1, together with the katanin MEI-1, is required for oocyte meiotic spindle pole assembly. MEI-1 recruits ASPM-1 to the spindle and also severs microtubules; both activities contribute to spindle bipolarity. Temperature-sensitive alleles, live-cell imaging, genetic epistasis Molecular biology of the cell High 24554763
2015 Drosophila Asp localizes to minus ends of spindle microtubule bundles and focuses them at poles independent of Ncd. An identified domain in Asp has microtubule cross-linking activity in vitro. Asp also localizes to minus ends of intraspindle augmin-dependent microtubules and focuses them toward poles during spindle flux. In vitro microtubule cross-linking assay, RNAi depletion, live-cell imaging, domain analysis The Journal of cell biology High 26644514
2015 ASPM interacts with the Cdk2/Cyclin E complex and modulates Cyclin E ubiquitination and phosphorylation, thereby regulating nuclear translocation of Cyclin E and the timing of restriction point passage in neural progenitors. ASPM-mutant mice show premature neural progenitor pool exhaustion due to shortened G1 before the restriction point. ASPM knock-in mouse model, co-immunoprecipitation, ubiquitination assay, cell cycle analysis Nature communications High 26581405
2017 ASPM forms a complex with the microtubule-severing ATPase katanin (p60/p80 heterodimer). X-ray crystallography revealed that the N- and C-terminal domains of katanin p60 and p80, respectively, bind conserved motifs in ASPM. Reconstitution experiments showed ASPM autonomously tracks growing microtubule minus ends and inhibits their growth; katanin potentiates this minus-end blocking and, together with ASPM, promotes microtubule severing. ASPM and katanin localize to spindle poles in a mutually dependent manner and regulate spindle flux. X-ray crystallography, in vitro microtubule reconstitution, TIRF microscopy, co-immunoprecipitation, siRNA knockdown Nature cell biology High 28436967
2017 Human ASPM functions redundantly with CDK5RAP2 (CEP215) in spindle pole focusing; ASPM gene knockout alone does not disrupt spindle morphology, but ASPM KO combined with CDK5RAP2 depletion causes spindle pole unfocusing during prometaphase and delayed anaphase onset. A microcephaly-associated hypomorphic ASPM mutation similarly caused pole unfocusing only in the absence of CDK5RAP2. CRISPR-based gene knockout, auxin-inducible degron, siRNA, live-cell imaging Journal of cell science High 28883092
2018 ASPM interacts with Disheveled-3 (Dvl-3), an upstream regulator of canonical Wnt signaling, and inhibits its proteasome-dependent degradation, thereby increasing Dvl-3 protein stability and enabling Wnt-induced β-catenin transcriptional activity in prostate cancer cells. ASPM depletion reduces ALDH+ cancer stem cell numbers and inhibits tumorigenicity. Co-immunoprecipitation, proteasome inhibitor rescue, siRNA knockdown, tumorigenicity assay Oncogene High 30266990
2021 ASPM is recruited to DNA double-strand break (DSB) sites in a PARP2-dependent manner. ASPM interacts with BRCA1 and its E3 ubiquitin ligase HERC2; ASPM prevents HERC2 from accessing BRCA1, thereby maintaining BRCA1 stability and enabling homologous recombination (HR) repair. ASPM inhibition promotes HERC2-mediated BRCA1 degradation, reduces HR efficiency, and sensitizes cells to ionizing radiation. Co-immunoprecipitation, PARP2 knockdown, HERC2 ubiquitination assay, HR repair assay, irradiation sensitivity iScience High 34142045
2022 ASPM is enriched at stalled replication forks in a RAD17-dependent manner and promotes RAD9 and TopBP1 loading onto chromatin, facilitating ATR-CHK1 checkpoint activation. ASPM depletion causes failed fork restart, MRE11-mediated nascent DNA degradation at stalled forks, chromosomal instability, and sensitization to replication stressors. iPOND (isolation of proteins on nascent DNA), chromatin fractionation, ATR-CHK1 phosphorylation assay, DNA fiber assay, siRNA knockdown Proceedings of the National Academy of Sciences of the United States of America High 36161901
2021 ASPM combined with KIF11 promotes hepatocellular carcinoma progression via the Wnt/β-catenin signaling pathway. Co-immunoprecipitation demonstrated a direct interaction between ASPM and KIF11; KIF11 overexpression rescued the proliferation/invasion defects caused by ASPM knockdown. Co-immunoprecipitation, siRNA knockdown, rescue overexpression, Western blot for β-catenin pathway Experimental and therapeutic medicine Medium 34504599
2011 ASPM downregulation by siRNA impairs DNA double-strand break repair (as measured by constant-field gel electrophoresis and γ-H2AX foci) in human cell lines, and IR sensitization by ASPM knockdown is not enhanced in DNA-PK-deficient cells, indicating ASPM acts in a DNA-PK-dependent (NHEJ) pathway. siRNA knockdown, constant-field gel electrophoresis, γ-H2AX foci analysis, radiosensitivity assay in DNA-PK-deficient cells International journal of radiation biology Medium 21923303
2021 METTL3-mediated N6-methyladenosine (m6A) modification of ASPM mRNA promotes ASPM expression in hepatocellular carcinoma. MeRIP validated the m6A modification on ASPM mRNA; METTL3 silencing suppressed cell proliferation/invasion, which was rescued by ASPM overexpression. MeRIP (methylated RNA immunoprecipitation), siRNA knockdown, rescue overexpression Journal of clinical laboratory analysis Medium 34398984
2021 In gastric cancer, ASPM isoform I (ASPMiI) interacts with DVL3 and together with FOXM1 controls β-catenin nuclear translocation and Wnt transcriptional activity through a multi-mode module: FOXM1 transcriptionally activates ASPM, ASPMiI stabilizes DVL3 via protein-protein interaction, and FOXM1 promotes β-catenin nuclear translocation. Co-immunoprecipitation, luciferase Wnt reporter, ChIP, siRNA knockdown, isoform-specific expression analysis Gastric cancer Medium 33515163
2024 RBM10 wild-type promotes ASPM exon 18 skipping by interacting with splicing factor SRSF2. RBM10 C761Y mutation impairs its interaction with SRSF2, generating the exon18-containing ASPM isoform (ASPM203) which stabilizes DVL2 and enhances β-catenin signaling to promote cholangiocarcinoma progression. Minigene splicing reporter, co-immunoprecipitation, RNA sequencing, siRNA/overexpression functional assays Journal of experimental & clinical cancer research Medium 38576051

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Identification of a novel aspartic protease (Asp 2) as beta-secretase. Molecular and cellular neurosciences 938 10656250
1995 Structure and function of ASP, the human homolog of the mouse agouti gene. Human molecular genetics 159 7757071
2008 Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA (New York, N.Y.) 140 18567810
2004 Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion. PLoS biology 140 15045028
2003 Protein-truncating mutations in ASPM cause variable reduction in brain size. American journal of human genetics 139 14574646
2001 The drosophila protein asp is involved in microtubule organization during spindle formation and cytokinesis. The Journal of cell biology 131 11352927
2017 Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex. Nature cell biology 129 28436967
1998 Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. Journal of lipid research 121 9555951
2001 Polo kinase and Asp are needed to promote the mitotic organizing activity of centrosomes. Nature cell biology 109 11283617
2018 ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-β-catenin signaling. Oncogene 105 30266990
2010 Human ASPM participates in spindle organisation, spindle orientation and cytokinesis. BMC cell biology 97 21044324
1999 Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Seminars in cell & developmental biology 91 10355026
2015 ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination. Nature communications 83 26581405
2008 The molecular landscape of ASPM mutations in primary microcephaly. Journal of medical genetics 83 19028728
2002 Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice. The Journal of biological chemistry 83 12244109
2011 ASPM regulates Wnt signaling pathway activity in the developing brain. Genes & development 82 21937711
2005 The abnormal spindle-like, microcephaly-associated (ASPM) gene encodes a centrosomal protein. Cell cycle (Georgetown, Tex.) 82 16123590
2005 Spindle pole organization in Drosophila S2 cells by dynein, abnormal spindle protein (Asp), and KLP10A. Molecular biology of the cell 80 15888542
2007 ASPM and citron kinase co-localize to the midbody ring during cytokinesis. Cell cycle (Georgetown, Tex.) 77 17534152
1992 The Ser-Arg-Tyr-Asp region of the major surface glycoprotein of Leishmania mimics the Arg-Gly-Asp-Ser cell attachment region of fibronectin. The Journal of biological chemistry 73 1629196
1997 Acylation-stimulating protein (ASP) regulates glucose transport in the rat L6 muscle cell line. Biochimica et biophysica acta 70 9059512
2010 ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target. Cancer cell international 69 20142996
2001 STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity. Oncogene 66 11494148
1999 Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice. The Journal of biological chemistry 64 10593909
2008 Primary microcephaly with ASPM mutation shows simplified cortical gyration with antero-posterior gradient pre- and post-natally. American journal of medical genetics. Part A 63 18452193
2005 ASPM mutations identified in patients with primary microcephaly and seizures. Journal of medical genetics 62 16141009
2004 Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations. Clinical genetics 60 15355437
2018 Autosomal recessive primary microcephaly due to ASPM mutations: An update. Human mutation 57 29243349
2015 Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice. Development (Cambridge, England) 57 26450969
1990 Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase. Nucleic acids research 56 1699202
2006 Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: Novel sequence variants in ASPM gene. Neurogenetics 52 16673149
1996 Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin. Protein science : a publication of the Protein Society 48 8845758
2002 Catalytic mechanism of S-adenosylhomocysteine hydrolase. Site-directed mutagenesis of Asp-130, Lys-185, Asp-189, and Asn-190. The Journal of biological chemistry 45 11927587
1994 Site-directed mutagenesis of the Asp-197 and Asp-202 residues in chitinase A1 of Bacillus circulans WL-12. Bioscience, biotechnology, and biochemistry 44 7765724
2018 Overexpression of the ASPM gene is associated with aggressiveness and poor outcome in bladder cancer. Oncology letters 42 30675249
2014 Caenorhabditis elegans oocyte meiotic spindle pole assembly requires microtubule severing and the calponin homology domain protein ASPM-1. Molecular biology of the cell 42 24554763
2023 Exploring Kinase Asp-Phe-Gly (DFG) Loop Conformational Stability with AlphaFold2-RAVE. Journal of chemical information and modeling 41 37981824
2009 Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation. Molecular immunology 41 19767107
2015 Microcephaly protein Asp focuses the minus ends of spindle microtubules at the pole and within the spindle. The Journal of cell biology 38 26644514
2020 ASPM promotes glioblastoma growth by regulating G1 restriction point progression and Wnt-β-catenin signaling. Aging 37 31905171
2013 Disruption of Aspm causes microcephaly with abnormal neuronal differentiation. Brain & development 36 24220505
2011 ASPM influences DNA double-strand break repair and represents a potential target for radiotherapy. International journal of radiation biology 35 21923303
2000 His-Asp phosphorelay signaling: a communication avenue between plants and their environment. Plant molecular biology 35 10794527
2014 Deregulation of microcephalin and ASPM expression are correlated with epithelial ovarian cancer progression. PloS one 34 24830737
2015 The HIV-1 antisense protein (ASP) induces CD8 T cell responses during chronic infection. Retrovirology 33 25809376
1998 Plasma acylation stimulating protein (ASP) as a predictor of impaired cellular biological response to ASP in patients with hyperapoB. European journal of clinical investigation 32 9767372
1994 The adipsin-ASP pathway and regulation of adipocyte function. Annals of medicine 32 7695862
2012 The microtubule-associated protein ASPM regulates spindle assembly and meiotic progression in mouse oocytes. PloS one 31 23152892
2001 Involvement of the Arg-Asp-His catalytic triad in enzymatic cleavage of the phosphodiester bond. Biochemistry 31 11331006
2021 ASPM promotes homologous recombination-mediated DNA repair by safeguarding BRCA1 stability. iScience 30 34142045
2005 Glu-Q-tRNA(Asp) synthetase coded by the yadB gene, a new paralog of aminoacyl-tRNA synthetase that glutamylates tRNA(Asp) anticodon. Biochimie 30 16164993
2010 Influence of Lβ-, Dα- and Dβ-Asp isomers of the Asp-76 residue on the properties of αA-crystallin 70-88 peptide. Amino acids 28 20437187
2017 Human microcephaly ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2. Journal of cell science 27 28883092
2001 Acylation stimulating protein (ASP) acute effects on postprandial lipemia and food intake in rodents. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 26 11360154
2008 Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans. Biochemical and biophysical research communications 25 18331833
2007 The ASP receptor C5L2 is regulated by metabolic hormones associated with insulin resistance. Biochemistry and cell biology = Biochimie et biologie cellulaire 25 17464341
2007 Novel protein-truncating mutations in the ASPM gene in families with autosomal recessive primary microcephaly. Journal of neurogenetics 25 17849285
1999 [Cytotoxic activity and cytokine gene induction of Asp-hemolysin to murine macrophages]. Nihon Ishinkin Gakkai zasshi = Japanese journal of medical mycology 25 10536308
2020 Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas. Journal of cellular and molecular medicine 24 32667745
2000 High sensitivity bioassay of paralytic (PSP) and amnesic (ASP) algal toxins based on the fluorimetric detection of [Ca(2+)](i) in rat cortical primary cultures. Toxicon : official journal of the International Society on Toxinology 24 10736481
2014 Molecular cloning and functional characterization of porcine DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41). Developmental and comparative immunology 23 25086295
2011 The microcephaly gene aspm is involved in brain development in zebrafish. Biochemical and biophysical research communications 23 21620798
2021 METTL3-mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis. Journal of clinical laboratory analysis 22 34398984
2002 A family of activation associated secreted protein (ASP) homologues of Cooperia punctata. Research in veterinary science 22 12443689
2012 Positive selection at the ASPM gene coincides with brain size enlargements in cetaceans. Proceedings. Biological sciences 21 22977148
2023 Oncogenic ASPM Is a Regulatory Hub of Developmental and Stemness Signaling in Cancers. Cancer research 20 37384617
2022 ASPM promotes ATR-CHK1 activation and stabilizes stalled replication forks in response to replication stress. Proceedings of the National Academy of Sciences of the United States of America 20 36161901
2016 Isomerization of Asp residues plays an important role in αA-crystallin dissociation. The FEBS journal 20 26700637
2012 Isomerization of Asp-Asp motif in model peptides and a monoclonal antibody Fab fragment. Journal of pharmaceutical sciences 20 23280575
2020 Venomics of the asp viper Vipera aspis aspis from France. Journal of proteomics 19 32087377
2020 Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4. Journal of Cancer 19 32742488
2011 Loss of ASP but not ROPN1 reduces mammalian ciliary motility. Cytoskeleton (Hoboken, N.J.) 19 22021175
2021 A multi-mode Wnt- and stemness-regulatory module dictated by FOXM1 and ASPM isoform I in gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 18 33515163
2019 Detection of antisense protein (ASP) RNA transcripts in individuals infected with human immunodeficiency virus type 1 (HIV-1). The Journal of general virology 18 30896385
2019 Site-specific analysis of the Asp- and Glu-ADP-ribosylated proteome by quantitative mass spectrometry. Methods in enzymology 18 31606080
2016 A novel splice-site mutation in the ASPM gene underlies autosomal recessive primary microcephaly. Annals of Saudi medicine 18 27920410
2012 The derived allele of ASPM is associated with lexical tone perception. PloS one 18 22529908
2009 Mutation analysis of the ASPM gene in 18 Pakistani families with autosomal recessive primary microcephaly. Journal of child neurology 18 19808985
2002 Murine calmodulin binding protein 1 (Calmbp1): tissue-specific expression during development and in adult tissues. Mechanisms of development 18 12351193
1999 A critical evaluation of the putative role of C3adesArg (ASP) in lipid metabolism and hyperapobetalipoproteinemia. Molecular immunology 18 10698341
2019 LPS-induced inflammation delays the transportation of ASP+ due to down-regulation of OCTN1/2 in alveolar epithelial cells. Journal of drug targeting 17 31591905
2022 Anticancer Properties of N,N-dibenzylasparagine as an Asparagine (Asp) analog, Using Colon Cancer Caco-2 Cell Line. Asian Pacific journal of cancer prevention : APJCP 16 35901362
2022 Deciphering the Alphabet of Disorder-Glu and Asp Act Differently on Local but Not Global Properties. Biomolecules 16 36291634
2021 ASPM combined with KIF11 promotes the malignant progression of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway. Experimental and therapeutic medicine 16 34504599
2023 The Multiple Mitotic Roles of the ASPM Orthologous Proteins: Insight into the Etiology of ASPM-Dependent Microcephaly. Cells 15 36980263
2022 Anti-Inflammatory and Mineralization Effects of an ASP/PLGA-ASP/ACP/PLLA-PLGA Composite Membrane as a Dental Pulp Capping Agent. Journal of functional biomaterials 15 35997444
2023 Horizontal gene transfer underlies the painful stings of asp caterpillars (Lepidoptera: Megalopygidae). Proceedings of the National Academy of Sciences of the United States of America 14 37428925
2020 A Pilot Study of the Humoral Response Against the AntiSense Protein (ASP) in HIV-1-Infected Patients. Frontiers in microbiology 14 32117090
2020 Australian snakebite myotoxicity (ASP-23). Clinical toxicology (Philadelphia, Pa.) 14 33156703
2023 The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM. Frontiers in neuroscience 13 37599996
2021 The HIV-1 Antisense Gene ASP: The New Kid on the Block. Vaccines 13 34067514
2020 A truncating Aspm allele leads to a complex cognitive phenotype and region-specific reductions in parvalbuminergic neurons. Translational psychiatry 13 32066665
2021 Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway. Bioengineered 12 34229534
2010 Hormone and pharmaceutical regulation of ASP production in 3T3-L1 adipocytes. Journal of cellular biochemistry 12 20069551
2001 [Cytotoxic activity and cytokine gene induction of Asp-hemolysin to vascular endothelial cells]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 12 11305044
2024 Caspase cleavage of RIPK3 after Asp333 is dispensable for mouse embryogenesis. Cell death and differentiation 11 38191748
2024 RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma. Journal of experimental & clinical cancer research : CR 11 38576051
2017 The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg-Gly-Asp motif. The Journal of biological chemistry 11 28882889
2008 Dual regulation with Ser/Thr kinase cascade and a His/Asp TCS in Myxococcus xanthus. Advances in experimental medicine and biology 11 18792684
2007 Sensitive and reliable detection of Kit point mutation Asp 816 to Val in pathological material. Diagnostic pathology 11 17900365