Affinage

ASPM

Abnormal spindle-like microcephaly-associated protein · UniProt Q8IZT6

Length
3477 aa
Mass
409.8 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASPM is a large IQ-domain scaffold protein that controls mitotic spindle organization in neural progenitors and thereby sets cerebral cortical size, originally identified as the human ortholog of Drosophila abnormal spindle and as a recurrent cause of autosomal recessive primary microcephaly (MCPH) (PMID:12355089, PMID:21044324). It concentrates at centrosomes/spindle poles in interphase and mitosis and at the midbody during cytokinesis, with its N-terminus directing centrosomal/spindle-pole localization and its disease-critical C-terminus directing midbody localization (PMID:15972725, PMID:17534152). Mechanistically, ASPM autonomously tracks growing microtubule minus ends and inhibits their growth; it forms a structurally defined complex with the severing ATPase katanin (p60/p80), mutually depends on katanin for spindle-pole accumulation, and recruits katanin to promote microtubule severing and spindle flux (PMID:28436967). It focuses spindle poles redundantly with CDK5RAP2 (PMID:28883092) and organizes astral microtubules and spindle orientation through citron kinase, which it recruits to the spindle (PMID:27562601). ASPM maintains the symmetric proliferative divisions and ventricular-surface affinity of radial glia, so its loss shifts progenitors toward premature neurogenic/asymmetric divisions and reduces cortical surface area in mouse and ferret models (PMID:16798874, PMID:29643508). Beyond spindle architecture, ASPM associates with WDR62 at the mother centriole to support centriole biogenesis and apical complex integrity (PMID:27974163), gates G1/S progression via the Cdk2/Cyclin E complex (PMID:26581405), and is essential for germline development, with a human ASPM transgene rescuing mouse microcephaly and germ-cell loss (PMID:20823249). ASPM additionally functions in genome maintenance: it acts in DNA-PK-dependent double-strand-break repair, protects BRCA1 from HERC2-mediated degradation to sustain homologous recombination, and is loaded at stalled replication forks in a RAD17-dependent manner to promote RAD9/TopBP1 chromatin loading and ATR-CHK1 checkpoint activation (PMID:21923303, PMID:34142045, PMID:36161901). In cancer, ASPM (notably exon-18-containing isoform 1) stabilizes oncogenic effectors by competing with their E3 ligases or autophagic turnover, including Dishevelled proteins to potentiate Wnt/β-catenin signaling, GLI1, NICD1, and FOXM1 (PMID:30266990, PMID:34428354, PMID:36638332, PMID:38279565, PMID:40122889).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Established ASPM's identity and the founding hypothesis that brain size is governed by spindle activity in neuronal progenitors, by linking it to MCPH and to the Drosophila spindle gene asp.

    Evidence Genetic mapping and mutation analysis in microcephaly patients with comparative protein-domain and mouse expression analysis

    PMID:12355089

    Open questions at the time
    • No biochemical activity or direct partner defined
    • Mechanism connecting spindle function to progenitor fate not yet shown
  2. 2005 High

    Localized ASPM to centrosomes and spindle poles and mapped its domain architecture (CH domains plus ~81 IQ repeats), placing it physically at the mitotic apparatus.

    Evidence Immunostaining of cultured human cells with N- and C-terminal antibodies plus isoform RT-PCR

    PMID:15972725

    Open questions at the time
    • Function of IQ repeats and CH domains untested
    • No interacting partner identified
  3. 2006 High

    Connected ASPM spindle-pole localization to cell-fate by showing its loss reorients the cleavage plane and depletes the progenitor pool, linking spindle orientation to neurogenesis.

    Evidence RNAi in mouse embryonic neuroepithelium with cleavage-plane and cell-fate tracking

    PMID:16798874

    Open questions at the time
    • Molecular mechanism of spindle-pole anchoring unknown
    • Direct microtubule activity not demonstrated
  4. 2007 Medium

    Resolved a functional division of labor within ASPM and added citron kinase as a midbody partner, explaining why C-terminal truncations are pathogenic.

    Evidence Reciprocal co-IP with CITK and GFP-fragment localization in HeLa and neuroepithelium

    PMID:17534152

    Open questions at the time
    • Functional consequence of the CITK interaction not yet tested
    • Single lab
  5. 2009 High

    Defined a conserved spindle-pole module (LIN-5/ASPM-1/calmodulin) acting through dynein independently of cortical Gα signaling, generalizing ASPM's spindle-pole role to meiosis.

    Evidence C. elegans genetic epistasis, co-IP, and live imaging

    PMID:19219036

    Open questions at the time
    • Direct human orthology of the LIN-5 partnership not shown
    • Biochemical mechanism of pole accumulation unresolved
  6. 2010 High

    Showed ASPM is a microtubule-dependent minus-end-associated pericentriolar protein required for spindle orientation and cytokinesis, and that its extreme C-terminus is essential, providing mechanistic basis for MCPH mutations.

    Evidence siRNA, live imaging, patient-fibroblast and dominant-negative fragment analysis in U2OS; transgenic mouse rescue with human ASPM

    PMID:20823249 PMID:21044324

    Open questions at the time
    • Direct microtubule-binding biochemistry not yet reconstituted
    • Mechanism of minus-end recognition unknown
  7. 2011 Medium

    Extended ASPM beyond the spindle by linking it to Wnt signaling, BRCA1 stability, DSB repair, and a UBE3A interaction, suggesting multifunctional roles.

    Evidence In utero electroporation with Wnt reporter/β-catenin rescue; siRNA with γ-H2AX and DNA-PK-deficient cells; yeast two-hybrid for UBE3A

    PMID:16123590 PMID:21633703 PMID:21923303 PMID:21937711

    Open questions at the time
    • UBE3A interaction lacks reciprocal co-IP (Low confidence)
    • Direct molecular link between ASPM and Wnt machinery not yet defined
    • BRCA1 reduction was single-method observation
  8. 2015 High

    Separated ASPM's spindle-orientation function from a distinct cell-cycle role, showing it gates G1 restriction-point timing via Cyclin E and mitigates DNA damage in dividing progenitors.

    Evidence Mouse Aspm mutants, co-IP, Cyclin E ubiquitination/phosphorylation assays; conditional KO with γ-H2AX and Bax/p53 epistasis in cerebellar progenitors and medulloblastoma

    PMID:26450969 PMID:26581405

    Open questions at the time
    • How ASPM modulates Cyclin E ubiquitination biochemically unresolved
    • Link between mitotic and DNA-damage functions unclear
  9. 2016 High

    Placed ASPM into two cortical-development modules: a centriolar WDR62 complex for centriole biogenesis and apical integrity, and a CITK-dependent astral-microtubule pathway controlling spindle orientation.

    Evidence Reciprocal co-IP, mass spectrometry, single/double KO mice for WDR62; cross-species siRNA, rescue, and MT-drug treatment for CITK

    PMID:27562601 PMID:27974163

    Open questions at the time
    • Hierarchy among centriolar partners only partly resolved
    • Direct astral MT-regulating activity of ASPM not biochemically isolated
  10. 2017 High

    Provided the definitive biochemical mechanism: ASPM tracks and blocks microtubule minus-end growth and forms a structurally defined complex with katanin to control severing and spindle flux, and focuses poles redundantly with CDK5RAP2.

    Evidence X-ray crystallography, in vitro reconstitution and MT-dynamics assays; CRISPR KO with auxin-degron CDK5RAP2 depletion and patient-mutation validation

    PMID:28436967 PMID:28883092

    Open questions at the time
    • How minus-end tracking integrates with pole focusing in vivo not fully mapped
    • Redundancy partners beyond CDK5RAP2 unexplored
  11. 2018 High

    Demonstrated in a gyrencephalic species that ASPM expands cortex by controlling radial-glia attachment to the ventricular surface, and refined its prostate-cancer Wnt role to Dishevelled stabilization.

    Evidence Germline Aspm KO ferret with cortical cell-type tracing; co-IP, proteasome inhibition and β-catenin reporter for Dvl-3

    PMID:29643508 PMID:30266990

    Open questions at the time
    • Molecular signal linking spindle/centriole function to surface affinity unknown
    • How ASPM shields Dvl-3 from the proteasome not defined
  12. 2022 High

    Defined ASPM's genome-maintenance mechanism at forks and breaks, showing RAD17-dependent fork loading driving ATR-CHK1 activation and BRCA1 protection from HERC2 to sustain homologous recombination.

    Evidence iPOND, DNA fiber, chromatin fractionation and CHK1 assays; co-IP with BRCA1/HERC2 and DR-GFP HR reporter with PARPi synergy

    PMID:34142045 PMID:36161901

    Open questions at the time
    • How a spindle-pole protein is recruited to chromatin/forks structurally unclear
    • Relationship between mitotic and DNA-repair pools of ASPM unresolved
  13. 2024 Medium

    Elaborated a recurring oncogenic theme in which ASPM (often exon-18 isoform 1) stabilizes oncoproteins by competing with their degradation machinery, spanning GLI1, NICD1, FOXM1, and Dvl2.

    Evidence Co-IP, ubiquitination and proteasomal/autophagic degradation assays, LLPS, ChIP-seq, and xenografts across SCLC, HCC, and glioma

    PMID:32667745 PMID:34428354 PMID:36638332 PMID:38279565 PMID:40122889

    Open questions at the time
    • Whether E3-ligase competition reflects a single shared biochemical mechanism unknown
    • Several interactions are single-lab co-IP based
    • Isoform-specificity not validated across all targets

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ASPM's defined microtubule minus-end/katanin activity mechanistically connects to its diverse non-spindle functions (Cyclin E gating, fork/break repair, Wnt and oncoprotein stabilization), and whether these reflect distinct protein pools or a unifying scaffolding principle.
  • No structural model linking the IQ-repeat scaffold to its many partners
  • Isoform-specific functional partitioning incompletely mapped
  • Mechanism of chromatin/fork recruitment of a centrosomal protein undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005815 microtubule organizing center 4 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
BRCA1CCNE1CDK5RAP2CITDVL3HERC2KATNA1WDR62
Complex memberships
ASPM-WDR62 centriolar complexASPM-katanin (p60/p80) complexLIN-5/ASPM-1/calmodulin spindle-pole complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 ASPM is the human ortholog of the Drosophila abnormal spindle gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. The mouse Aspm gene is expressed specifically in primary sites of prenatal cerebral cortical neurogenesis. ASPM proteins encode systematically larger numbers of IQ domains between flies, mice and humans, suggesting brain size is controlled in part through modulation of mitotic spindle activity in neuronal progenitor cells. Genetic mapping, mutation analysis in MCPH patients, comparative genomic/protein domain analysis, mouse expression studies Nature genetics High 12355089
2005 Human ASPM protein localizes to the spindle poles during mitosis in cultured human cells, as determined by immunostaining with antibodies to both N- and C-termini. ASPM contains two N-terminal calponin-homology (CH) domains and a large block of IQ domains; the major isoform contains 81 IQ domains organized into a higher-order repeat structure. Immunostaining of cultured human cells, Western blot with peptide-specific antibodies, RT-PCR for isoform characterization Human molecular genetics High 15972725
2005 ASPM localizes to the centrosome in interphase and to spindle poles from prophase through telophase. siRNA-mediated downregulation of ASPM decreases protein levels of endogenous BRCA1. siRNA knockdown, immunofluorescence, Western blot Cell cycle Medium 16123590
2006 Aspm is concentrated at mitotic spindle poles of mouse embryonic neuroepithelial (NE) cells and is down-regulated as these cells switch from proliferative to neurogenic divisions. RNAi knockdown of Aspm in telencephalic NE cells reduces Aspm at spindle poles, causes the cleavage plane to deviate from perpendicular to the ventricular surface, increases asymmetric divisions (apical membrane inherited by only one daughter), and results in reduction of the NE progenitor pool and premature neurogenesis. RNA interference in mouse embryonic brain, immunofluorescence, cleavage plane orientation analysis, BrdU/cell fate tracking Proceedings of the National Academy of Sciences of the United States of America High 16798874
2007 ASPM co-localizes with citron kinase (CITK) at the midbody ring during cytokinesis in mammalian cells and embryonic neuroepithelium, and co-immunoprecipitates with CITK in HeLa cell lysates and embryonic neuroepithelium. A GFP-tagged N-terminal ASPM fragment localizes to centrosomes and spindle poles, while a C-terminal fragment localizes to midbodies. All reported microcephaly-causing ASPM mutations involve truncation or mutation of the C-terminus. Co-immunoprecipitation, GFP-fragment localization, immunofluorescence co-localization Cell cycle Medium 17534152
2009 In C. elegans, ASPM-1 (the ASPM ortholog) is a novel LIN-5 (NuMA-related) binding partner. ASPM-1, together with calmodulin (CMD-1), promotes meiotic spindle organization and accumulation of LIN-5 at meiotic and mitotic spindle poles. Meiotic spindle rotation requires LIN-5, ASPM-1, CMD-1, and dynein, but is independent of the GPR-1/2/Gα cortical pathway, defining a distinct LIN-5/ASPM-1/CMD-1 spindle pole complex. Genetic epistasis in C. elegans, co-immunoprecipitation, live-cell imaging, RNAi Nature cell biology High 19219036
2010 Human ASPM is a microtubule minus-end associated protein recruited in a microtubule-dependent manner to the pericentriolar matrix at spindle poles during mitosis. siRNA depletion of ASPM in U2OS cells perturbs mitotic spindle orientation, and the majority of ASPM-depleted cells fail to complete cytokinesis. A pathogenic MCPH splice-site mutation produces a variant protein lacking a tripeptide motif, dramatically reducing ASPM spindle pole localization. Expression of dominant-negative C-terminal ASPM fragments causes spindle assembly defects and cytokinesis failure. The extreme C-terminus is required for ASPM localization and function. siRNA knockdown, immunofluorescence, live-cell imaging, patient fibroblast analysis, dominant-negative fragment expression BMC cell biology High 21044324
2010 In Aspm mutant mice, truncated Aspm proteins fail to localize to the midbody during M-phase and cause mild microcephaly and massive germ cell loss (reduced testis/ovary size, reduced fertility). A human ASPM transgene rescues both the microcephaly and germline phenotypes, demonstrating conserved function between mouse and human ASPM. Aspm mutant mouse generation, human ASPM transgene rescue, immunofluorescence for midbody localization, histology Proceedings of the National Academy of Sciences of the United States of America High 20823249
2011 Knockdown of Aspm in developing mouse brain results in decreased Wnt-mediated transcription, and expression of stabilized β-catenin rescues this deficit and rescues in vivo neurogenesis/migration defects caused by Aspm knockdown. ASPM acts as a positive regulator of Wnt signaling in the developing brain. In utero electroporation, Wnt reporter assay, β-catenin rescue, in vivo cortical analysis Genes & development Medium 21937711
2011 UBE3A (Angelman syndrome E3 ubiquitin ligase) was identified as an ASPM interactor by yeast two-hybrid screen of a human fetal brain cDNA library. Both ASPM and UBE3A localize to the centrosome. shRNA knockdown of UBE3A leads to mitotic abnormalities including chromosome missegregation and abnormal cytokinesis. Yeast two-hybrid, immunofluorescence co-localization, shRNA knockdown PloS one Low 21633703
2012 In mouse oocytes, ASPM localizes to the entire meiotic spindle at metaphase I and II, co-localizing with acetylated tubulin. Morpholino-mediated knockdown of ASPM causes abnormal meiotic spindle assembly and blocks meiotic progression at metaphase I with elongated spindles. Co-immunoprecipitation combined with mass spectrometry revealed that ASPM interacts with calmodulin in MI oocytes, and the two proteins co-localize at the spindle. Immunofluorescence, morpholino knockdown, co-immunoprecipitation, mass spectrometry, taxol/nocodazole treatment PloS one Medium 23152892
2014 In C. elegans oocytes, ASPM-1 (calponin-homology domain protein) is required for normal bipolar meiotic spindle pole assembly. MEI-1 (katanin) recruits ASPM-1 to the spindle and microtubule severing by MEI-1 both contribute to monopolar spindle assembly in klp-18 (kinesin-12) mutants. aspm-1 loss results in bipolar but abnormal meiotic spindles. Temperature-sensitive allele isolation, live-cell imaging, C. elegans genetics Molecular biology of the cell Medium 24554763
2015 ASPM regulates symmetric stem cell division through an interaction with the Cdk2/Cyclin E complex. ASPM modulates Cyclin E ubiquitination, phosphorylation, and nuclear localization, thereby controlling the length of time neural progenitors spend in early G1 before traversing the restriction point, independently of mitotic spindle orientation effects. Mouse Aspm mutant model, co-immunoprecipitation, cell cycle analysis, Cyclin E ubiquitination/phosphorylation assays Nature communications Medium 26581405
2015 Aspm regulates mitosis and mitigates DNA damage during cerebellar granule neuron progenitor (CGNP) cell division. Genetic deletion of Aspm reduces cerebellar growth, increases mitotic rate, causes impaired mitotic progression, altered division orientation/differentiation, and increased DNA damage leading to progenitor apoptosis. Deletion of Aspm in Smo-induced medulloblastoma reduces tumor growth and increases DNA damage; co-deletion with Bax or Trp53 rescues neural progenitor survival. Conditional Aspm knockout mice, medulloblastoma mouse model, γ-H2AX staining, genetic epistasis with Bax/p53 Development High 26450969
2016 Aspm and Wdr62 physically interact and both localize to the proximal end of the mother centriole. Wdr62 is required for Aspm localization. Both proteins, along with Cep63, are required to localize CENPJ/CPAP/Sas-4 at centrioles. Loss of either protein causes centriole duplication defects. Aspm and Wdr62 are also required for normal apical complex localization and apical epithelial structure, promoting premature delamination and precocious differentiation of neural progenitors. Co-immunoprecipitation, immunofluorescence, mouse single and double knockouts, mass spectrometry interactome Neuron High 27974163
2016 ASPM controls spindle orientation by interacting with citron kinase (CITK). ASPM recruits CITK to the spindle, and CITK overexpression rescues the spindle orientation defect caused by ASPM loss. Both ASPM and CITK affect astral microtubule organization; low doses of a microtubule-stabilizing drug revert the spindle orientation phenotype caused by their knockdown. CITK regulates both astral MT nucleation and stability. siRNA knockdown in mouse cortex and Drosophila, immunofluorescence, astral MT analysis, CITK overexpression rescue, MT-stabilizing drug treatment EMBO reports High 27562601
2017 ASPM forms a complex with katanin (the microcephaly-associated microtubule-severing ATPase) through conserved motifs: X-ray crystallography revealed the heterodimer of katanin p60 N-terminal and p80 C-terminal domains binds conserved motifs in ASPM. ASPM autonomously tracks growing microtubule minus ends and inhibits their growth. Katanin decorates and bends microtubule ends and potentiates ASPM minus-end blocking activity. ASPM recruits katanin along microtubules and promotes katanin-mediated microtubule severing. ASPM and katanin localize to spindle poles in a mutually dependent manner and regulate spindle flux. X-ray crystallography, reconstitution experiments, in vitro microtubule dynamics assays, immunofluorescence, mass spectrometry Nature cell biology High 28436967
2017 Human ASPM functions in spindle pole organization during mitotic metaphase redundantly with CDK5RAP2. Deletion of ASPM alone does not affect spindle morphology, but when CDK5RAP2 is depleted in ASPM KO cells, spindle poles are unfocused during prometaphase and anaphase onset is significantly delayed. A hypomorphic patient mutation in ASPM similarly caused spindle pole unfocusing in the absence of CDK5RAP2. CRISPR-based gene knockout, auxin-inducible degron for CDK5RAP2 depletion, live-cell imaging, patient mutation analysis Journal of cell science High 28883092
2018 Aspm knockout in ferrets causes severe microcephaly (25-40% reduction in brain weight) reflecting reduced cortical surface area without significant change in cortical thickness, mirroring human patients. Fetal Aspm KO ferret cortex displays large premature displacement of ventricular radial glial cells (vRGCs) to the outer subventricular zone where they resemble outer radial glia. This suggests ASPM regulates cortical expansion by controlling the affinity of vRGCs for the ventricular surface, modulating the ratio of vRGCs to outer radial glia. Genome editing (germline Aspm KO in ferret), histology, immunofluorescence, cortical cell type analysis Nature High 29643508
2018 ASPM interacts with disheveled-3 (Dvl-3), a canonical upstream regulator of 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. This mechanism maintains a cancer stem cell (ALDH+) subpopulation. Co-immunoprecipitation, proteasome inhibitor experiments, β-catenin reporter assay, siRNA knockdown, ALDH+ CSC quantification Oncogene Medium 30266990
2008 Hepatitis C virus NS5A protein down-regulates ASPM mRNA and protein expression via the PKR-p38 signaling pathway. NS5A represses the ASPM promoter in a dose-dependent manner; amino acid substitutions in NS5A that disrupt NS5A-PKR interaction abolish this effect. Overexpression of ASPM relieves the G2/M cell cycle block induced by NS5A, and NS5A expression causes chromosome aneuploidy. In vivo hydrodynamics-based transfection, laser capture microdissection, microarray, qPCR, Western blot, promoter reporter assay, NS5A mutants, ASPM overexpression rescue The Journal of biological chemistry Medium 18728014
2011 ASPM knockdown by siRNA impairs DNA double-strand break (DSB) repair in irradiated human cells, as shown by constant-field gel electrophoresis and γ-H2AX foci analysis, and elevates abnormal chromosomes. IR-sensitization by ASPM knockdown was not enhanced in DNA-PK-deficient glioblastoma cells, indicating ASPM impacts the DNA-PK-dependent (NHEJ) pathway. siRNA knockdown, constant-field gel electrophoresis, γ-H2AX foci analysis, clonogenic survival assay, DNA-PK-deficient cell line International journal of radiation biology Medium 21923303
2021 ASPM is recruited to DNA damage sites in a PARP2-dependent manner and interacts with BRCA1 and its E3 ligase HERC2. ASPM prevents HERC2 from accessing BRCA1, thereby protecting BRCA1 from degradation and ensuring efficient homologous recombination (HR) repair. ASPM inhibition promotes HERC2-mediated BRCA1 degradation, compromises HR efficiency and chromosome stability, and sensitizes cancer cells to ionizing radiation. Synergy between ASPM inhibition and PARP inhibition was observed. Co-immunoprecipitation, HR efficiency assay (DR-GFP reporter), γ-H2AX/RAD51 foci, ASPM siRNA, PARP inhibitor combination assay iScience Medium 34142045
2021 ASPM interacts with disheveled-2 (Dvl2) and antagonizes autophagy-mediated Dvl2 degradation by weakening the interaction between Dvl2 and LC3II, thereby increasing Dvl2 protein abundance and activating Wnt/β-catenin signaling in hepatocellular carcinoma cells. Co-immunoprecipitation, autophagy inhibition, LC3II interaction assay, Wnt reporter assay, siRNA knockdown, xenograft model FEBS open bio Medium 34428354
2022 ASPM is enriched at stalled replication forks in a RAD17-dependent manner in response to replication stress. ASPM promotes RAD9 and TopBP1 loading onto chromatin, facilitating ATR-CHK1 checkpoint activation. ASPM depletion results in failed fork restart and MRE11-mediated nascent DNA degradation at stalled forks, causing chromosome instability. DNA fiber assay, iPOND (replication fork isolation), chromatin fractionation, siRNA knockdown, RAD17-dependent localization, CHK1 phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 36161901
2023 ASPM isoform 1 (ASPM-I1, containing exon 18) stabilizes the Hedgehog transcriptional factor GLI1 at the protein level through a unique exon-18-encoded region by competing with E3 ligases β-TrCP and CUL3, preventing GLI1 proteasomal degradation. In parallel, ASPM-I1 sustains SMO transcription through the Wnt-DVL3-β-catenin signaling axis in small cell lung cancer cells. Reporter array screening, co-immunoprecipitation, ubiquitination assay, GLI1 proteasomal degradation assay, SMO transcription analysis, in vivo xenograft Cancer research Medium 36638332
2024 ASPM isoform 1 (ASPM-i1) interacts with NOTCH1 intracellular domain (NICD1) and competes with FBXW7 (E3 ubiquitin ligase) binding to NICD1, blocking FBXW7-mediated polyubiquitination and proteasomal degradation of NICD1, thereby stabilizing NICD1 and activating Notch signaling in hepatocellular carcinoma cells. Co-immunoprecipitation, ubiquitination assay, FBXW7-binding-deficient NICD1 mutant, siRNA knockdown rescue, tissue co-expression analysis Molecular oncology Medium 38279565
2024 ASPM interacts with FOXM1 protein via liquid-liquid phase separation (LLPS), enhancing FOXM1 stability by preventing proteasome-mediated degradation. ASPM and FOXM1 co-occupy promoters of multiple genes (ChIP-seq). FOXM1 also transcriptionally activates ASPM expression, forming a positive feedback loop in hepatocellular carcinoma cells. LLPS assay, co-immunoprecipitation, ChIP-sequencing, proteasomal degradation assay, luciferase reporter, xenograft model Genome biology Medium 40122889
2021 ASPM interacts with KIF11 (Eg5 kinesin) in HCC cells as demonstrated by co-immunoprecipitation. ASPM in combination with KIF11 promotes HCC malignant progression via the Wnt/β-catenin signaling pathway; ASPM knockdown effects on proliferation, invasion, and migration are rescued by KIF11 overexpression. Co-immunoprecipitation, siRNA knockdown, KIF11 overexpression rescue, Western blot for Wnt pathway components Experimental and therapeutic medicine Low 34504599
2023 ASPM inhibits ubiquitin-mediated degradation of KIF11 through direct binding, stabilizing KIF11 protein in anaplastic thyroid carcinoma cells. KO of ASPM reduces KIF11 protein levels and inhibits EMT and tumor migration/invasion. Co-immunoprecipitation, ubiquitination assay, ASPM knockout (CRISPR), Western blot, xenograft model Cell biology international Low 36883909
2021 METTL3-mediated N6-methyladenosine (m6A) modification of ASPM mRNA promotes ASPM expression in liver hepatocellular carcinoma. Silencing METTL3 suppresses HCC cell proliferation, migration, and invasion, and this is rescued by ASPM overexpression. MeRIP (m6A immunoprecipitation), METTL3 knockdown, ASPM rescue overexpression, Western blot, cell functional assays Journal of clinical laboratory analysis Low 34398984
2020 FoxM1 transcription factor directly binds the ASPM promoter at specific sites (-236 to -230 bp and -1354 to -1348 bp) and activates ASPM transcription, as confirmed by ChIP and dual-luciferase reporter assay. ASPM mediates FoxM1-driven proliferation and migration in glioma cells. ChIP, dual-luciferase reporter assay, siRNA knockdown, FoxM1 overexpression Journal of cellular and molecular medicine Medium 32667745

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proceedings of the National Academy of Sciences of the United States of America 495 17090670
2002 ASPM is a major determinant of cerebral cortical size. Nature genetics 451 12355089
2006 Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proceedings of the National Academy of Sciences of the United States of America 331 16798874
2005 Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science (New York, N.Y.) 197 16151010
2005 The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Human molecular genetics 170 15972725
2010 Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline. Proceedings of the National Academy of Sciences of the United States of America 156 20823249
2004 Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Human molecular genetics 155 14722158
2003 Evolution of the human ASPM gene, a major determinant of brain size. Genetics 147 14704186
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
2017 Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex. Nature cell biology 131 28436967
2018 Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size. Nature 129 29643508
2017 Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease. Protein & cell 123 29058117
2016 Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate. Neuron 116 27974163
2018 ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-β-catenin signaling. Oncogene 111 30266990
2009 NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Galpha. Nature cell biology 109 19219036
2010 Human ASPM participates in spindle organisation, spindle orientation and cytokinesis. BMC cell biology 100 21044324
2006 A novel domain suggests a ciliary function for ASPM, a brain size determining gene. Bioinformatics (Oxford, England) 99 16443634
2009 Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations. Neurology 91 19770472
2015 ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination. Nature communications 86 26581405
2011 ASPM regulates Wnt signaling pathway activity in the developing brain. Genes & development 85 21937711
2005 The abnormal spindle-like, microcephaly-associated (ASPM) gene encodes a centrosomal protein. Cell cycle (Georgetown, Tex.) 84 16123590
2008 The molecular landscape of ASPM mutations in primary microcephaly. Journal of medical genetics 83 19028728
2006 Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans". Science (New York, N.Y.) 83 16840683
2007 ASPM and citron kinase co-localize to the midbody ring during cytokinesis. Cell cycle (Georgetown, Tex.) 79 17534152
2010 ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target. Cancer cell international 70 20142996
2011 ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival. British journal of cancer 66 21505456
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 65 18452193
2005 ASPM mutations identified in patients with primary microcephaly and seizures. Journal of medical genetics 62 16141009
2018 Autosomal recessive primary microcephaly due to ASPM mutations: An update. Human mutation 60 29243349
2004 Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations. Clinical genetics 60 15355437
2016 ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules. EMBO reports 58 27562601
2015 Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice. Development (Cambridge, England) 58 26450969
2006 Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: Novel sequence variants in ASPM gene. Neurogenetics 52 16673149
2018 Overexpression of the ASPM gene is associated with aggressiveness and poor outcome in bladder cancer. Oncology letters 45 30675249
2008 Hepatitis C virus NS5A protein down-regulates the expression of spindle gene Aspm through PKR-p38 signaling pathway. The Journal of biological chemistry 45 18728014
2014 Caenorhabditis elegans oocyte meiotic spindle pole assembly requires microtubule severing and the calponin homology domain protein ASPM-1. Molecular biology of the cell 43 24554763
2006 Normal variants of Microcephalin and ASPM do not account for brain size variability. Human molecular genetics 42 16687438
2023 ASPM Activates Hedgehog and Wnt Signaling to Promote Small Cell Lung Cancer Stemness and Progression. Cancer research 40 36638332
2020 ASPM promotes glioblastoma growth by regulating G1 restriction point progression and Wnt-β-catenin signaling. Aging 39 31905171
2013 Disruption of Aspm causes microcephaly with abnormal neuronal differentiation. Brain & development 37 24220505
2014 Deregulation of microcephalin and ASPM expression are correlated with epithelial ovarian cancer progression. PloS one 36 24830737
2011 ASPM influences DNA double-strand break repair and represents a potential target for radiotherapy. International journal of radiation biology 36 21923303
2008 Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas. Oncology reports 36 18636190
2021 ASPM promotes hepatocellular carcinoma progression by activating Wnt/β-catenin signaling through antagonizing autophagy-mediated Dvl2 degradation. FEBS open bio 35 34428354
2021 ASPM promotes homologous recombination-mediated DNA repair by safeguarding BRCA1 stability. iScience 32 34142045
2020 An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ, and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan. Molecular genetics & genomic medicine 32 32677750
2012 The microtubule-associated protein ASPM regulates spindle assembly and meiotic progression in mouse oocytes. PloS one 31 23152892
2004 A translocation breakpoint disrupts the ASPM gene in a patient with primary microcephaly. European journal of human genetics : EJHG 30 14997185
2015 Genome-wide analysis of the oxyntic proliferative isthmus zone reveals ASPM as a possible gastric stem/progenitor cell marker over-expressed in cancer. The Journal of pathology 29 26178168
2017 Human microcephaly ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2. Journal of cell science 28 28883092
2016 Molecular and phenotypic spectrum of ASPM-related primary microcephaly: Identification of eight novel mutations. American journal of medical genetics. Part A 28 27250695
2008 Positive selection in ASPM is correlated with cerebral cortex evolution across primates but not with whole-brain size. Molecular biology and evolution 26 18718919
2007 Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens". Science (New York, N.Y.) 26 17446375
2008 Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans. Biochemical and biophysical research communications 25 18331833
2007 Novel protein-truncating mutations in the ASPM gene in families with autosomal recessive primary microcephaly. Journal of neurogenetics 25 17849285
2021 METTL3-mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis. Journal of clinical laboratory analysis 24 34398984
2020 Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas. Journal of cellular and molecular medicine 24 32667745
2011 The microcephaly gene aspm is involved in brain development in zebrafish. Biochemical and biophysical research communications 24 21620798
2007 No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism. Biology letters 24 17251122
2023 Oncogenic ASPM Is a Regulatory Hub of Developmental and Stemness Signaling in Cancers. Cancer research 23 37384617
2011 Angelman syndrome protein UBE3A interacts with primary microcephaly protein ASPM, localizes to centrosomes and regulates chromosome segregation. PloS one 23 21633703
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 21 36161901
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 21 33515163
2012 Positive selection at the ASPM gene coincides with brain size enlargements in cetaceans. Proceedings. Biological sciences 21 22977148
2009 Compound heterozygous ASPM mutations associated with microcephaly and simplified cortical gyration in a consanguineous Algerian family. European journal of medical genetics 21 19332161
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
2021 Whole Exome Sequencing Identifies Three Novel Mutations in the ASPM Gene From Saudi Families Leading to Primary Microcephaly. Frontiers in pediatrics 18 33643967
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
2023 The Multiple Mitotic Roles of the ASPM Orthologous Proteins: Insight into the Etiology of ASPM-Dependent Microcephaly. Cells 17 36980263
2021 ASPM combined with KIF11 promotes the malignant progression of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway. Experimental and therapeutic medicine 17 34504599
2015 Enhancement of tumor initiation and expression of KCNMA1, MORF4L2 and ASPM genes in the adenocarcinoma of lung xenograft after vorinostat treatment. Oncotarget 17 25796627
2021 ASPM facilitates colorectal cancer cells migration and invasion by enhancing β-catenin expression and nuclear translocation. The Kaohsiung journal of medical sciences 16 34741399
2020 A truncating Aspm allele leads to a complex cognitive phenotype and region-specific reductions in parvalbuminergic neurons. Translational psychiatry 14 32066665
2013 Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory. Clinical genetics 14 23611254
2023 The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM. Frontiers in neuroscience 13 37599996
2017 Molecular genetic analysis of consanguineous families with primary microcephaly identified pathogenic variants in the ASPM gene. Journal of genetics 13 28674240
2024 RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma. Journal of experimental & clinical cancer research : CR 11 38576051
2023 ASPM promotes migration and invasion of anaplastic thyroid carcinoma by stabilizing KIF11. Cell biology international 11 36883909
2022 Whole exome sequencing identifies a novel mutation in ASPM and ultra-rare mutation in CDK5RAP2 causing Primary microcephaly in consanguineous Pakistani families. Pakistan journal of medical sciences 11 35035405
2018 Primary microcephaly caused by novel compound heterozygous mutations in ASPM. Human genome variation 11 29644084
2021 Updates on Clinical and Genetic Heterogeneity of ASPM in 12 Autosomal Recessive Primary Microcephaly Families in Pakistani Population. Frontiers in pediatrics 10 34295862
2024 ASPM stabilizes the NOTCH intracellular domain 1 and promotes oncogenesis by blocking FBXW7 binding in hepatocellular carcinoma cells. Molecular oncology 9 38279565
2021 ASPM is a Novel Candidate Gene Associated with Colorectal Cancer Cell Growth. DNA and cell biology 9 34042518
2021 Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ. Genes 9 34068194
2025 ASPM mediates nuclear entrapment of FOXM1 via liquid-liquid phase separation to promote progression of hepatocarcinoma. Genome biology 8 40122889
2022 ASPM Promotes the Progression of Anaplastic Thyroid Carcinomas by Regulating the Wnt/β-Catenin Signaling Pathway. International journal of endocrinology 8 35387319
2021 Novel Pathogenic Mutation Mapping of ASPM Gene in Consanguineous Pakistani Families with Primary Microcephaly. Brazilian journal of biology = Revista brasleira de biologia 8 34378666
2021 Mutation screening of multiple Pakistani MCPH families revealed novel and recurrent protein-truncating mutations of ASPM. Biotechnology and applied biochemistry 8 34826358
2022 Loss of abnormal spindle-like, microcephaly-associated (Aspm) disrupts female folliculogenesis in mice during maturation and aging. Reproductive biology 7 35901620
2021 Two New Cases of Primary Microcephaly with Neuronal Migration Defect Caused by Truncating Mutations in the ASPM Gene. Molecular syndromology 7 35221876
2017 Whole exome sequencing identifies a novel homozygous frameshift mutation in the ASPM gene, which causes microcephaly 5, primary, autosomal recessive. F1000Research 7 29375817
2005 Expression of IQ-motif genes in human cells and ASPM domain structure. Ethnicity & disease 7 16315386
2024 Nrf2/ASPM axis regulated vasculogenic mimicry formation in hepatocellular carcinoma under hypoxia. Journal of gastroenterology 6 39097533
2024 Asp/ASPM phospho-regulation throughout the cell cycle. Genome 6 39471460
2022 Autosomal Recessive Primary Microcephaly (MCPH) and Novel Pathogenic Variants in ASPM and WDR62 Genes. Molecular syndromology 6 36588751
2017 Longitudinal Diffusion Tensor Imaging Revealed Nerve Fiber Alterations in Aspm Mutated Microcephaly Model Mice. Neuroscience 6 29253521

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