| 2001 |
NUCKS1 (then called P1/NUCKS) is a nuclear phosphoprotein that serves as a substrate for Cdk1 during mitosis; phosphopeptide mapping and back-phosphorylation experiments using HeLa interphase and metaphase cell-derived protein demonstrated mitosis-specific phosphorylation of threonine residues by Cdk1. |
Phosphopeptide mapping, back-phosphorylation assays, molecular cloning |
European journal of biochemistry |
High |
11298763
|
| 2002 |
NUCKS1 contains a putative DNA-binding domain with an extended GRP motif that forms an alpha helix and fits into the major groove of DNA via basic residues; phosphorylation of the Cdk1 site within this domain completely abolishes DNA binding in vitro. |
Synthetic peptide DNA-binding assay, NMR structural analysis, docking modeling, in vitro phosphorylation |
Archives of biochemistry and biophysics |
Medium |
12413487
|
| 2004 |
The NUCKS1 protein is a vertebrate-specific protein whose fish ortholog is also a substrate for CDK1 and CK-2 in vitro, indicating conserved kinase substrate function across vertebrates. The gene lacks a TATA box but contains Inr elements, GC boxes, and an E2F-1 binding site. |
In vitro kinase assay, Western immunoblotting, database searches |
Biochemical and biophysical research communications |
Medium |
15381070
|
| 2007 |
NUCKS1 contains two functional nuclear localization signals (NLS1 and NLS2); NLS1 is the primary bipartite NLS and is required for nuclear import. NLS1 mediates binding to importin alpha3 and importin alpha5 in vitro, indicating receptor-mediated nuclear import. A splice variant lacking NLS1 fails to enter the nucleus. |
GFP-fusion subcellular localization, site-directed mutagenesis, GFP-immunoprecipitation, GST pull-down, immunofluorescence |
Biochimica et biophysica acta |
High |
17604136
|
| 2008 |
NUCKS1 is one of the most heavily post-translationally modified proteins known; SILAC-based quantitative proteomics identified 25 phosphorylation sites (6 novel), plus multiple acetylation, methylation, and formylation sites. Cell-cycle-dependent changes include increased phosphorylation and decreased acetylation in mitotically arrested cells. At least 36 of 243 residues can be modified (57 PTMs total). |
SILAC quantitative proteomics, mass spectrometry, phosphopeptide mapping |
Proteins |
High |
18491381
|
| 2014 |
NUCKS1 functions as a transcriptional activator of the insulin receptor (IR) and other insulin signaling components by regulating chromatin accessibility and RNA Pol II recruitment to their promoters. NUCKS1 knockout mice show impaired insulin signaling, obesity, glucose intolerance and insulin resistance, phenotypes worsened by high-fat diet. |
Genome-wide ChIP-seq, NUCKS1 knockout mouse, glucose/insulin tolerance tests, knockdown in endocrine cells |
Cell reports |
High |
24931609
|
| 2014 |
NUCKS1 physically interacts with HIV-1 Tat protein (identified by yeast two-hybrid and confirmed by co-immunoprecipitation) and acts as a Tat coactivator; NUCKS1 knockdown reduces Tat accumulation at the TAR region of the HIV-1 LTR (by ChIP assay) and diminishes viral transcription and replication, without affecting Tat nuclear localization or Cyclin T1 interaction. |
Yeast two-hybrid, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assay, siRNA knockdown |
Retrovirology |
Medium |
25116364
|
| 2015 |
NUCKS1 shares extensive sequence homology with RAD51AP1 and functions as a paralog in homologous recombination (HR) DNA repair; NUCKS1 depletion impairs HR, increases sensitivity to mitomycin C, increases chromatid breaks, and slows replication fork progression with increased new origin firing. Recombinant NUCKS1 binds DNA with the same preference as RAD51AP1 but with lower affinity. |
siRNA knockdown, HR assay, chromatid break analysis, DNA fiber assay, recombinant protein DNA-binding assay, MMC sensitivity assay |
Nucleic acids research |
High |
26323318
|
| 2015 |
Hypothalamic NUCKS1 specifically regulates peripheral glucose homeostasis and insulin signaling; hypothalamus-specific NUCKS1 knockout mice show glucose intolerance on normal chow and exacerbated obesity and insulin resistance on high-fat diet, while immune-cell-specific NUCKS1 knockout does not produce these phenotypes. |
Conditional tissue-specific Cre-lox knockout mice (Nkx2.1-Cre), glucose tolerance test, insulin tolerance test, intracerebroventricular insulin injection |
The Biochemical journal |
High |
26205492
|
| 2016 |
NUCKS1 is phosphorylated on 11 sites by CK2 (at least 7 confirmed in vivo) and on two sites by ATM kinase and DNA-PK in vitro; ATM-mediated phosphorylation of NUCKS1 occurs in vivo in gamma-irradiated cells, linking NUCKS1 to the DNA damage response via PIKK kinases. |
In vitro and in vivo phosphorylation assays, mass spectrometry, phosphopeptide mapping, phosphoamino acid analysis, phosphospecific antibodies, kinase inhibitors |
Biochimica et biophysica acta. Proteins and proteomics |
High |
28011258
|
| 2016 |
In a Trp53-deficient background, loss of one Nucks1 allele accelerates radiation-induced thymic lymphoma development in mice, and wild-type Nucks1 levels are required to suppress radiation-induced lymphomagenesis, consistent with NUCKS1 functioning in the DNA damage response as a tumor suppressor. |
Mouse genetics (Trp53+/- Nucks1+/- compound mutant), X-irradiation, tumor analysis, LOH analysis, flow cytometry |
Oncotarget |
Medium |
27542204
|
| 2017 |
NUCKS1 regulates NF-κB-mediated cytokine expression in corneal epithelial cells; NUCKS1 knockout reduces LPS-induced NF-κB activation and downstream expression of IL6, IP10, and TNFα in vitro, and suppresses inflammation and neovascularization in an in vivo corneal alkali burn model. |
NUCKS1 knockout mice, alkali burn model, in vitro LPS-NF-κB assay, cytokine profiling, siRNA silencing |
Scientific reports |
Medium |
28106169
|
| 2019 |
NUCKS1 promotes gastric cancer cell proliferation and invasion via transcriptional upregulation of IGF-1R, which activates the PI3K/Akt/mTOR pathway; IGF-1R knockdown eliminates the pro-tumorigenic effects of NUCKS1 overexpression, placing NUCKS1 upstream of IGF-1R/PI3K/Akt/mTOR signaling. |
siRNA knockdown, ectopic overexpression, xenograft mouse model, Western blotting, cell invasion/proliferation assays |
Carcinogenesis |
Medium |
30371738
|
| 2020 |
NUCKS1 physically and functionally interacts with the DNA motor protein RAD54; NUCKS1 stimulates the ATPase activity of RAD54 and the RAD51-RAD54-mediated strand invasion step during D-loop formation in vitro. In cells, NUCKS1 controls resolution of RAD54 foci after DNA damage and prevents inappropriate engagement of RAD54 with RAD51AP1 in unperturbed cells. |
Co-immunoprecipitation, in vitro ATPase assay, in vitro D-loop assay, focus formation/resolution assay, cell-based DNA damage assays |
The Journal of cell biology |
High |
32876692
|
| 2020 |
NUCKS1 knockdown in gastric cancer cells induces autophagy through the mTOR-Beclin1 pathway; this autophagy induction is rescued by NUCKS1 restoration, and Beclin1 silencing in NUCKS1-knockdown cells, or rapamycin treatment in NUCKS1-overexpressing cells, confirms NUCKS1 acts upstream of mTOR to suppress Beclin1-dependent autophagy. |
siRNA knockdown, genetic rescue, rapamycin treatment, Western blotting, autophagy assays, xenograft |
Journal of experimental & clinical cancer research |
Medium |
32958058
|
| 2020 |
NUCKS1 physically interacts with CDK1 (verified by co-immunoprecipitation) and promotes CDK1 expression in NSCLC cells; CDK1 knockdown or inhibition alleviates the pro-proliferative and pro-invasive effects of NUCKS1 overexpression. |
Co-immunoprecipitation, shRNA knockdown, CDK1 inhibitor, cell proliferation/invasion assays, xenograft |
Cancer management and research |
Medium |
33380837
|
| 2021 |
NUCKS1 functions as a transcription factor that is recruited to chromatin in response to mitogenic stimulation to activate SKP2 expression, leading to degradation of p21 and p27 and S phase entry. DNA damage induces p53-dependent transcriptional repression of NUCKS1, causing SKP2 downregulation, p21/p27 accumulation, and cell cycle arrest (NUCKS1-SKP2-p21/p27 axis). |
ChIP, siRNA/shRNA knockdown, reporter assay, cell cycle analysis, epistasis by genetic manipulation of each component |
Nature communications |
High |
34845229
|
| 2023 |
NUCKS1 transcriptionally upregulates asparagine synthetase (ASNS), elevating asparagine levels in osteosarcoma cells to promote proliferation and metastasis; ASNS inhibition or asparagine reduction diminishes the pro-tumorigenic effects of NUCKS1. |
siRNA knockdown, overexpression, asparagine measurement, ASNS inhibition, xenograft, in vitro functional assays |
Cell death & disease |
Medium |
37528150
|
| 2024 |
NUCB2 interacts with NUCKS1 protein to inhibit its degradation (stabilization), which in turn allows NUCKS1 to transcriptionally upregulate CXCL8 expression in osteosarcoma, promoting PD-L1 expression and immunosuppression. |
Co-immunoprecipitation, knockdown, Western blotting, reporter assay, in vivo tumor model |
Cancer letters |
Medium |
38636892
|
| 2025 |
NUCKS1 directly binds to the promoter of Cdc42 and transcriptionally upregulates Cdc42 expression in hepatocellular carcinoma, promoting cancer cell proliferation and migration; Cdc42 expression is positively correlated with NUCKS1 in HCC tissues. |
ChIP (promoter binding), siRNA knockdown, overexpression, in vitro and in vivo functional assays |
American journal of cancer research |
Medium |
40226459
|
| 2025 |
NUCKS1 stabilizes HDAC2 by inhibiting lysosomal degradation, leading to AKT activation and promotion of colorectal cancer invasion and metastasis; HDAC2 inhibition or AKT inhibition rescues the pro-metastatic effects of NUCKS1 overexpression both in vitro and in vivo. |
Knockdown/overexpression, HDAC2 inhibitor (Santacruzamate A), AKT inhibitor (LY294002), in vivo tail-vein metastasis model, Western blotting |
Oncogenesis |
Medium |
40527876
|
| 2025 |
NUCKS1 directly binds to the promoter of S100A9 and transcriptionally upregulates its expression in HNSCC, enhancing malignancy; NUCKS1 ablation decreases S100A9 promoter activity and expression. |
Promoter reporter assay, siRNA knockdown, overexpression, in vitro and in vivo functional assays |
Biochemical pharmacology |
Medium |
40946978
|
| 2026 |
DDX21 binds the NUCKS1 promoter and its downregulation reduces NUCKS1 transcription, leading to elevated p21/p27 levels and G0/G1 arrest in dormancy-like colorectal cancer cells; HERC2 mediates K48/K63-linked polyubiquitination and degradation of DDX21, placing DDX21 upstream of NUCKS1 in a HERC2-DDX21-NUCKS1-p21/p27 axis. |
Proteomics, ChIP (DDX21 binding to NUCKS1 promoter), ubiquitination assay, knockdown/overexpression, cell cycle analysis |
Cell death & disease |
Medium |
42071007
|