| 2017 |
NUSAP1 localizes to dynamic spindle microtubules in a chromosome-centric pattern near overlapping microtubules during metaphase and anaphase. Mass spectrometry identified a cell cycle-regulated interaction between NUSAP1 and the RanBP2-RanGAP1-UBC9 SUMO E3 ligase complex. The SAP domain of NUSAP1 is implicated in substrate recognition consistent with a co-factor role in sumoylation during chromosome segregation. |
Endogenous Co-IP, mass spectrometry, live cell imaging, siRNA knockdown with Taxol-sensitivity phenotype |
The Journal of biological chemistry |
High |
28900032
|
| 2023 |
NUSAP1 contains two consensus SUMOylation sites within its DNA-binding and microtubule-binding domains, respectively. Site-specific mutagenesis revealed that each site selectively controls NUSAP1 localization and generates distinct mitotic defects and daughter-cell fates. NUSAP1 forms proximity ligation products with SUMO2/3 in a RANBP2-dependent manner at key mitotic sites. |
Site-directed mutagenesis, proximity ligation assay, cell line expression of NuSAP1 mutants, mitotic phenotyping |
Cells |
High |
37947624
|
| 2020 |
NUSAP1 stabilizes ATR protein by promoting its sumoylation via the SAP domain, antagonizing ubiquitin-dependent proteolysis of ATR. The SAP domain of NUSAP1 was necessary for this sumoylation and for chemoresistance to TMZ and DOX in glioblastoma cells. |
Co-IP, sumoylation assay, ubiquitination assay, SAP domain deletion/mutation, siRNA knockdown, cell viability assay |
Signal transduction and targeted therapy |
Medium |
32317623
|
| 2023 |
NUSAP1 interacts with ILF2 and DHX9 (RNA-binding proteins). The microtubule-binding and charged helical domains of NUSAP1 are required for these protein-protein interactions. Depletion of NUSAP1 abolished ILF2-dependent suppression of R-loop accumulation and DNA damage in response to camptothecin, placing NUSAP1 upstream of ILF2 in DNA damage/R-loop regulation. |
Affinity purification-mass spectrometry, Co-IP, confocal colocalization, domain deletion analysis, siRNA knockdown with R-loop and DNA damage assays |
International journal of molecular sciences |
High |
37047232
|
| 2014 |
NUSAP1 depletion suppresses double-strand DNA break repair via homologous recombination and single-strand annealing pathways, and causes centrosome duplication defects. These phenotypes are mediated through BRCA1 protein levels: NUSAP1 depletion decreases BRCA1 protein and reduces BRCA1 recruitment to ionizing radiation-induced foci; BRCA1 overexpression from a plasmid rescues the defects caused by NUSAP1 depletion. |
siRNA knockdown, DNA repair assays (HR, SSA), centrosome counting, immunofluorescence for BRCA1 foci, plasmid rescue experiment |
Cancer biology & therapy |
Medium |
24521615
|
| 2023 |
NUSAP1 binds to c-Myc and HIF-1α, forming a transcription regulatory complex that localizes to the LDHA promoter region and enhances LDHA expression. Lactate stabilizes NUSAP1 protein by inducing lysine lactylation (Kla) modification, inhibiting NUSAP1 protein degradation, creating a feedforward loop. |
ChIP-seq, Co-IP, RNA-seq, xenograft mouse model, single-cell RNA-seq, CHIP-seq verification of complex at LDHA promoter |
Cancer letters |
Medium |
37354982
|
| 2021 |
NUSAP1 functions as a positive regulator of YAP1 protein stability in gastric cancer cells. NUSAP1 was identified as a novel binding partner of YAP1 by Co-IP, and NUSAP1 depletion reduces YAP1 levels and downstream Hippo target gene transcription (CTGF, CYR61). Cancer-promoting effects of NUSAP1 on cell growth, migration and invasion are largely mediated through YAP1. |
Co-IP, siRNA knockdown, xenograft model, epistasis rescue (YAP1-dependent phenotype) |
Frontiers in oncology |
Medium |
33489890
|
| 2021 |
NUSAP1 interacts with CDC20 and CCNA2 (Cyclin A2) by co-immunoprecipitation in osteosarcoma cells. NUSAP1 accelerates cell proliferation and cell cycle progression, and silencing either CDC20 or CCNA2 inhibits NUSAP1-induced proliferation and cell cycle progression. |
Co-immunoprecipitation, siRNA knockdown, CCK-8 and EdU proliferation assays, flow cytometry, xenograft model |
OncoTargets and therapy |
Medium |
34079289
|
| 2022 |
NUSAP1 depletion in glioblastoma cells leads to downregulation of TOP2A, and silencing either NUSAP1 or TOP2A inhibits GBM cell proliferation and invasion and induces apoptosis. NUSAP1 expression is strongly correlated with TOP2A in glioma datasets, and stable NUSAP1 knockdown reduces tumor growth in an orthotopic xenograft model. |
RNA sequencing of NUSAP1-stable knockdown cells, siRNA knockdown of NUSAP1 and TOP2A, proliferation/invasion assays, orthotopic xenograft |
Cell cycle (Georgetown, Tex.) |
Medium |
35532155
|
| 2015 |
NUSAP1 expression is regulated by the RB1/E2F1 axis: RB1 knockdown increases NUSAP1 expression, and E2F1 knockdown decreases it. NUSAP1 knockdown in RB1-null or RB1-depleted prostate cancer cells decreases cell proliferation and invasion. |
Lentiviral RB1 knockdown, transient E2F1 siRNA, RT-qPCR, Western blot, proliferation and invasion assays |
The Prostate |
Medium |
25585568
|
| 2022 |
HOXB2 transcriptionally activates NUSAP1; dual-luciferase reporter and chromatin immunoprecipitation assays confirmed that HOXB2 binds the NUSAP1 promoter. HOXB2 overexpression abrogated the inhibitory effects of NUSAP1 silencing on nephroblastoma cell proliferation and metastasis via the PI3K/Akt signaling pathway. |
Dual-luciferase reporter assay, ChIP assay, JASPAR bioinformatics, Western blot for PI3K/Akt pathway proteins, siRNA and overexpression transfection |
Molecular medicine reports |
Medium |
35485274
|
| 2023 |
Transcription factor E2F8 directly binds the NUSAP1 promoter (confirmed by ChIP and dual-luciferase reporter) and regulates NUSAP1 transcription. The E2F8/NUSAP1 axis promotes cisplatin resistance in hepatocellular carcinoma by reducing DNA damage (γ-H2AX), with NUSAP1 knockdown sensitizing cells to cisplatin. |
ChIP assay, dual-luciferase reporter, siRNA knockdown, CCK-8, flow cytometry, comet assay, Western blot |
International journal of toxicology |
Medium |
37331996
|
| 2025 |
PRMT1 catalyzes asymmetric dimethylation of NUSAP1 at R418 and R422 (ADMA). The R422 methylation site is critical for NUSAP1 function: methylated NUSAP1 interacts with the PEST domain of Notch2, inhibiting Notch2 ubiquitination and stabilizing Notch2 protein to activate Notch2 signaling. Inhibition of PRMT1 or R422 mutation abolishes NUSAP1-mediated Notch2 stabilization and 5-FU resistance in gastric cancer. |
Proteomic analysis, site-directed mutagenesis, Co-IP, ubiquitination assay, Western blot, functional resistance assays |
Cell death & disease |
Medium |
40393971
|
| 2021 |
O-GlcNAcylation (mediated by OGT) enhances NUSAP1 protein stability in bladder cancer cells. Pharmacological upregulation of O-GlcNAc increases NUSAP1 protein levels and stability, and OGT knockdown reduces tumor growth, while NUSAP1 overexpression impairs this effect, placing NUSAP1 downstream of OGT-mediated O-GlcNAcylation. |
Western blot, pharmacological O-GlcNAc modulation (GlcNAc, PuGNAc), OGT siRNA, CCK-8, flow cytometry, xenograft |
OncoTargets and therapy |
Low |
33488099
|
| 2022 |
ANKRD22 regulates NUSAP1 expression, and NUSAP1 overexpression reverses the inhibitory effects of ANKRD22 knockdown on breast cancer cell proliferation, invasion, and EMT. NUSAP1 mediates ANKRD22 activation of the Wnt/β-catenin signaling pathway. |
siRNA knockdown, overexpression rescue assay, Western blot for β-catenin pathway, BrdU, colony formation, Transwell assays |
Bosnian journal of basic medical sciences |
Low |
32651974
|
| 2022 |
NUSAP1 promotes early recurrence of hepatocellular carcinoma by stimulating STAT3 nuclear translocation and activation through RACK1. RNA sequencing showed enrichment of cancer stemness and STAT3 pathway gene sets upon NUSAP1 overexpression. |
RNA sequencing, gain/loss-of-function experiments, in vivo recurrence mouse model, pathway analysis |
Cancer science |
Low |
36106345
|
| 2025 |
NUSAP1 functions as a tumor suppressor in triple-negative breast cancer by recruiting the transcriptional repressor DAXX via its microtubule-associated domain (MAD) to bridge HIFα. This complex recruits SETDB1 methyltransferase and deposits H3K9me3 repressive marks on hypoxia response elements (HREs), attenuating HIF transcriptional activity and expression of HIF target genes. |
NUSAP1 depletion/overexpression, in vitro and in vivo invasion/proliferation assays, Co-IP (NUSAP1-DAXX-HIFα), ChIP for H3K9me3 at HREs, engineered MAD domain rescue |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
41178464
|
| 2024 |
NUSAP1 interacts with ANXA2 (Annexin A2) and protects it from ubiquitin-dependent protein degradation, thereby increasing ANXA2 stability. NUSAP1 silencing increases GC radiosensitivity by impairing DNA damage repair after irradiation. |
Immunoprecipitation, mass spectrometry, ubiquitination assay, colony formation, flow cytometry, comet assay, xenograft |
Journal of cancer research and clinical oncology |
Medium |
39212774
|
| 2025 |
NUSAP1 interacts with SHCBP1 and inhibits JAK2/STAT3 phosphorylation by blocking SHCBP1 in hepatocellular carcinoma cells, promoting dendritic cell generation from co-cultured PBMCs. |
Co-immunoprecipitation, Western blot for phospho-JAK2/STAT3, PBMC co-culture with HCC cells, flow cytometry for CD1a/CD86 |
Journal of immunotherapy |
Low |
38980111
|
| 2025 |
NUSAP1 directly interacts with KIF2C (a kinesin-13 microtubule depolymerase) and Aurora kinase A (AURKA). AURKA-mediated phosphorylation of NUSAP1 modulates NUSAP1's binding affinity to KIF2C, balancing spindle microtubule stability and depolymerization. Truncating NUSAP1 mutations (Y403* and Q405*) impair NUSAP1-KIF2C interaction. NUSAP1 rescues cell cycle arrest and apoptosis caused by KIF2C overexpression in NUSAP1-KO cells, but mutant truncated NUSAP1 fails this rescue. |
Co-IP (NUSAP1-KIF2C, NUSAP1-AURKA), phosphorylation assay, NUSAP1-KO HEK293T rescue experiment, mouse microcephaly model, live cell imaging |
bioRxivpreprint |
Medium |
bio_10.1101_2025.05.16.654427
|
| 2023 |
A recurrent de novo heterozygous nonsense variant (p.Tyr403Ter) in NUSAP1 causes microcephaly, severe developmental delay, and epilepsy. The mutant transcript escapes nonsense-mediated decay, suggesting dominant-negative or gain-of-function mechanism rather than haploinsufficiency. |
Exome sequencing, NMD escape assay (transcript analysis), single-cell RNA-seq of post-mortem brain |
Clinical genetics |
Medium |
37005340
|
| 2019 |
In zebrafish, nusap1 morpholino knockdown impairs neural crest cell migration, alters expression of neural crest markers crestin and sox9b, and causes apoptosis in retina and hindbrain. These phenotypes are rescued by co-injection of nusap1 mRNA. This establishes an in vivo role for Nusap1 in cell migration and neural crest morphogenesis. |
Antisense morpholino knockdown in zebrafish, in situ hybridization for neural crest markers, mRNA rescue injection |
Protein & cell |
Medium |
21203972
|
| 2023 |
In mouse oocytes, NUSAP1 localizes to distinct granular aggregates near spindle poles during Pro-MI, metaphase I, and anaphase I. NUSAP1 depletion causes chromosome misalignment, increased aneuploidy, abnormal spindle assembly with decreased spindle pole width, and attenuation of cortical F-actin. Mass spectrometry of NUSAP1 interactomes showed significant enrichment for RNA-binding partners, suggesting NUSAP1 influences P-body dynamics and mRNA homeostasis. |
Protein expression profiling (proteomics), siRNA depletion, immunofluorescence for localization, aneuploidy measurement, RNA-seq, mass spectrometry interactome |
Journal of cellular biochemistry |
Medium |
37992207
|
| 2025 |
NUSAP1 interacts with NUSAP1-IP3R (inositol 1,4,5-trisphosphate receptor); NUSAP1 governs IP3R phosphorylation status to regulate cytosolic Ca2+ homeostasis and ER stress. NUSAP1 knockdown increases cytosolic Ca2+, p-IP3R, and ER stress, promoting mitophagy and apoptosis in endometrial carcinoma cells. IP3R silencing reduces Ca2+ and ER stress without affecting NUSAP1 expression, but NUSAP1 overexpression combined with IP3R knockdown amplified these effects synergistically. |
Co-IP (NUSAP1-IP3R interaction), Fluo-4 AM Ca2+ measurement, ER fluorescence probe imaging, flow cytometry, Western blot, siRNA knockdown and overexpression |
ACS omega |
Low |
41585655
|
| 2025 |
HBV core protein (HBC) enhances WDR46 protein stability by blocking TRIM25-mediated ubiquitination of WDR46. WDR46 then facilitates c-Myc recruitment to the NUSAP1 promoter by enhancing the WDR46-c-Myc interaction, thereby transcriptionally upregulating NUSAP1 to promote HCC cell growth and migration. |
Co-immunoprecipitation, ChIP, Western blot, ubiquitination assay, functional growth and migration assays, xenograft model |
Hepatology communications |
Medium |
40366140
|
| 2024 |
NUSAP1 promotes lung adenocarcinoma cell proliferation, and its upregulation is mediated by estrogen via ERβ activation. Pharmacological targeting of the ERβ/NUSAP1 axis with fulvestrant (ERβ antagonist) or entinostat (identified as a novel NUSAP1 inhibitor) suppresses LUAD growth in vitro and in vivo. |
Bioinformatics, in vitro proliferation assays with estrogen treatment, ERβ activation/inhibition, entinostat treatment, in vivo xenograft |
International journal of biological sciences |
Low |
39430250
|