| 2004 |
A nuclear isoform of cathepsin L, devoid of a signal peptide (translated from downstream AUG sites), localizes to the nucleus during the G1-S transition and proteolytically processes the CDP/CUX transcription factor to generate the p110 isoform, thereby regulating cell cycle progression. |
Immunofluorescence imaging, activity-based probe labeling, ectopic expression of cathepsin L, Cat L-/- cell analysis, in situ processing assays |
Molecular cell |
High |
15099520
|
| 2006 |
A 90 kDa CUX1 isoform (p90) is generated by cathepsin L proteolytic processing; its steady-state level correlates with cathepsin L activity, and it shares similar DNA-binding and transcriptional activities with p110. |
Deletion mapping, Western blot, co-expression with cathepsin L mutants |
Biological chemistry |
Medium |
16972798
|
| 2002 |
A shorter CUX1 isoform, p75, is generated by transcription initiation within intron 20 and contains only Cut repeat 3 and the Cut homeodomain; it can repress the p21 promoter and activate a DNA polymerase alpha reporter, and its aberrant expression in mammary epithelial cells is associated with altered differentiation. |
Reporter assays, stable cell expression, RT-PCR, cell morphology/collagen assays |
Cancer research |
Medium |
12438259
|
| 2006 |
The p110 CDP/CUX isoform accelerates entry into S phase by shortening G1 by 2-4 hours; it upregulates cyclin E2 and A2, and its loss in Cutl1z/z MEFs prolongs G1 and reduces proliferation. |
Stable cell populations with p110, synchronization experiments (growth factor deprivation, thymidine block, centrifugal elutriation), MEF genetic inactivation, focus formation and tumor growth assays |
Molecular and cellular biology |
High |
16508018
|
| 2008 |
p110 CUX1 cooperates with E2F1 and E2F2 in transcriptional activation of cell cycle genes including DNA polymerase alpha; p110 engages in protein-protein interactions with E2F1/E2F2, promotes their recruitment to target promoters, and a low-affinity E2F binding site is required for this activation. |
Tandem affinity purification, co-immunoprecipitation, chromatin immunoprecipitation, linker-scanning analysis, reporter assays, genome-wide location analysis |
Molecular and cellular biology |
High |
18347061
|
| 1999 |
CUX1/CDP is a component of NF-μNR and represses the immunoglobulin heavy chain intronic enhancer (Eμ) by binding to MAR sequences and antagonizing the Bright transcription activator at both the DNA-binding and functional levels. |
Expression library screening, EMSA, co-immunoprecipitation, antiserum recognition, cotransfection/reporter assays |
Molecular and cellular biology |
High |
9858552
|
| 1999 |
CUX1/CDP interacts with SATB1 through its Cut repeats (CR1, CR2, and homeodomain); this interaction prevents each protein from binding DNA and CUX1 overexpression in T cells neutralizes SATB1-mediated repression of the MMTV promoter. |
GST pull-down, co-immunoprecipitation with specific antisera, Far-Western blot, gel retardation assay, reporter assay |
Molecular and cellular biology |
High |
10373541
|
| 2014 |
CUX1 functions as an ancillary factor in base excision repair by directly stimulating the enzymatic activity of 8-oxoG-DNA glycosylase OGG1; Cux1+/- MEFs are haploinsufficient for repair of oxidative DNA damage, whereas elevated CUX1 accelerates repair. CUX1 prevents RAS-induced senescence and is synthetic lethal with oncogenic RAS. |
In vitro BER assay with purified proteins, single-cell gel electrophoresis (comet assay), MEF haploinsufficiency analysis, RNAi synthetic lethality, transgenic mouse models |
PLoS biology |
High |
24618719
|
| 2015 |
A single CUT repeat domain of CUX1 is sufficient to stimulate DNA binding, Schiff-base formation, glycosylase, and AP-lyase activities of OGG1; Cux1-/- MEFs cannot proliferate in 20% O2 but proliferate normally in 3% O2, rescued by ectopic CUX1 or a recombinant Cut repeat protein devoid of transcriptional activity. |
In vitro enzymatic assays with purified proteins, genetic rescue with structure-function constructs, MEF proliferation assays under different oxygen levels |
Oncotarget |
High |
25682875
|
| 2018 |
CUX1 CUT domains stimulate APE1 (apurinic/apyrimidinic endonuclease 1) enzymatic activity; CUX1 knockdown increases abasic sites and decreases APE1 activity in cell extracts, while CUX1 overexpression or a two-CUT-domain protein increases APE1 activity and resistance of glioblastoma cells to temozolomide. |
In vitro DNA repair assay with purified proteins, abasic site quantification in genomic DNA, cell extract APE1 activity assay, clonogenic survival with CUX1 KD/OE |
Neuro-oncology |
High |
29036362
|
| 2017 |
CUX1 is rapidly recruited to sites of DNA damage; a recombinant protein containing only two CUT domains is sufficient for this recruitment, accelerates DNA repair, and increases clonogenic survival following ionizing radiation. |
Clonogenic survival assay, CUX1 KD/OE, recombinant CUT domain protein rescue, DNA damage focus analysis |
Oncotarget |
Medium |
28147323
|
| 2012 |
CUX1 regulates the constitutive expression of ATM and ATR and genes involved in damage-induced signaling through them; CUX1 knockdown or genetic inactivation reduces ATM autophosphorylation, phospho-Chk2, p53 levels, γ-H2AX/Rad51 foci, and compromises DNA strand break repair and cell cycle checkpoints. |
RNAi knockdown, genetic inactivation, immunofluorescence for DNA damage foci, phosphoprotein analysis, genome-wide expression profiling |
Nucleic acids research |
Medium |
22319212
|
| 2010 |
CUX1 and CUX2 are intrinsic and complementary regulators of dendrite branching, spine development, and synapse formation in layer II-III cortical neurons; Cux genes control dendritic spine number and maturation partly through direct regulation of Xlr3b and Xlr4b expression, and Cux2-/- mice show reduced synaptic function and working memory defects. |
Knockout and knockdown mice, morphological, molecular, and electrophysiological analysis |
Neuron |
High |
20510857
|
| 2010 |
Increasing Cux1 (but not Cux2) expression reduces dendritic complexity of cortical pyramidal neurons, while reducing Cux1 promotes dendritic arborization; this effect requires the DNA-binding domains and acts primarily through suppression of p27Kip1, with RhoA as a downstream mediator. |
In vitro neuronal cultures with gain/loss of function, immunofluorescence for dendritic morphology, signaling pathway analysis |
PloS one |
Medium |
20485671
|
| 2009 |
Cux1 directly interacts with the co-repressor Grg4 (Groucho 4) to enhance repression of p27Kip1; both Cux1 and Grg4 (along with HDAC1 and HDAC3) are recruited to the p27Kip1 promoter in vivo, and Cux1 binds directly to the p27Kip1 promoter at two sites identified by DNase I footprinting. |
Co-immunoprecipitation, promoter luciferase assay, ChIP in kidney tissue, DNase I footprinting |
Gene |
High |
19332113
|
| 2020 |
CUX1 mediates the synergistic inflammatory response to TNF and IL-17A in synovial fibroblasts by binding a unique CUX1-NF-κB motif in the promoters of CXCL1, CXCL2, and CXCL3 and cooperating with NF-κB p65 to drive their transcription, independent of LIFR, STAT3, STAT4, and ELF3. |
Gene silencing transcriptomics, siRNA knockdown, promoter motif analysis, functional reporter assays |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
32079724
|
| 2009 |
CUX1 expression is induced by PI3K/Akt signaling and decreased by PI3K inhibitors; CUX1 exerts anti-apoptotic activity by upregulating BCL2 and downregulating TNFα, conferring resistance to TRAIL- and drug-induced apoptosis in pancreatic cancer cells. |
CUX1 overexpression and knockdown, Akt pathway activation/inhibition, caspase activity assays, PARP cleavage, xenograft model with siRNA nanoparticles |
Gut |
Medium |
20442202
|
| 2009 |
CUX1 regulates several Wnt genes and is involved in establishing a Wnt/β-catenin autocrine loop in mammary tumors; CUX1 transcriptionally regulates Wnt genes as demonstrated by ChIP, shRNA-mediated knockdown, and reporter assays. |
Chromatin immunoprecipitation, shRNA knockdown, reporter assays, transgenic mouse mammary tumor analysis |
Cancer research |
Medium |
19738070
|
| 2014 |
CUX1 and GLIS1 cooperate to stimulate TCF/β-catenin transcriptional activity and enhance cell migration and invasion; elevated WNT gene expression is associated with high CUX1 and GLIS1 and with EMT gene signatures. |
Co-expression experiments, TCF/β-catenin reporter assays, cell migration and invasion assays, expression profiling |
Biology open |
Medium |
25217618
|
| 2011 |
CUX1 acts as a negative regulator of TGF-β signaling-induced type I collagen transcription; CUX1 suppresses type I collagen through interference with gene transcription, and abnormal CUX1 expression is restored by TGF-β via the p38 MAPK pathway in fibroblasts. |
CUX1 overexpression/silencing in fibroblasts, in vivo fibrosis model, reporter/transcriptional interference assays, p38 inhibitor experiments |
Molecular biology of the cell |
Medium |
21471005
|
| 2021 |
CUX1 deficiency directly alleviates CUX1 repression of the CFLAR (FLIP) promoter, driving CFLAR expression and apoptosis evasion in AML; CFLAR is a selective vulnerability in CUX1-haploinsufficient AML identified by genome-wide CRISPR/Cas9 screening, and IAP antagonists exploit this vulnerability. |
Genome-wide CRISPR/Cas9 screen, promoter reporter assays, ChIP, murine and human AML models |
Nature communications |
High |
33931647
|
| 2019 |
p110 CUX1 (a transcription factor generated by proteolytic processing) promotes glycolytic gene expression (enolase 1, glucose-6-phosphate isomerase, phosphoglycerate kinase 1) in neuroblastoma; circ-CUX1 binds EWSR1 to facilitate EWSR1-MAZ interaction, resulting in transactivation of MAZ and CUX1 itself. |
Mechanistic RNA-protein binding assays, co-immunoprecipitation, inhibitory peptide blockade, lentiviral knockdown, metabolic assays |
EMBO molecular medicine |
Medium |
31709724
|
| 2021 |
A novel 113-aa protein (p113) encoded by the CUX1 circular RNA interacts with ZRF1 and BRD4 to form a transcriptional regulatory complex that upregulates ALDH3A1, NDUFA1, and NDUFAF5, driving lipid metabolic reprogramming and mitochondrial activity in neuroblastoma. |
Co-immunoprecipitation, mass spectrometry, ChIP sequencing, RNA sequencing, dual-luciferase reporter, inhibitory peptide blockade |
Molecular cancer |
Medium |
34579723
|
| 2022 |
CUX1 binds to an atherosclerosis-associated SNP (rs1537371) in the CDKN2A/B locus and regulates p14ARF, p15INK4b, p16INK4a, and ANRIL expression in endothelial cells; induction of CUX1 by DNA damage or oxidative stress triggers p16INK4a-dependent senescence. |
Post-GWAS functional SNP analysis, ChIP, CUX1 knockdown/overexpression, senescence assays |
Nature aging |
Medium |
37117763
|
| 2004 |
Cux-1 regulates the onset of joint formation by facilitating conversion of chondrocytes into nonchondrogenic interzone cells; retroviral Cux1 expression in micromass chondrocyte cultures causes loss of cartilage matrix and downregulation of cartilage-specific gene expression. |
Retroviral expression in micromass cultures, Alcian blue staining, gene expression analysis |
Developmental biology |
Medium |
11846476
|
| 2004 |
Cux-1 interacts with the Groucho homolog TLE-4 (a corepressor of Notch signaling) and is upregulated by constitutively active Notch 1 in renal epithelial cells, associated with reduction of p27, suggesting Cux-1 functions in the Notch signaling pathway. |
Coexpression analysis, activated Notch 1 cell line, co-immunoprecipitation (inferred), immunohistochemistry, RT-PCR |
Developmental dynamics |
Low |
15499562
|
| 2008 |
A deletion in the Cux1 cathepsin L processing site leads to accumulation of unprocessed Cux1, downregulation of p21/p27, and accelerated PKD progression in cpk mice; nuclear cathepsin L is reduced in human ADPKD cells and Pkd1 null kidneys, corresponding to increased Cux1 protein levels. |
Mouse genetic model (Cux1 mutant × cpk), Western blot, immunohistochemistry for proliferation/apoptosis/p21/p27, nuclear cathepsin L analysis in ADPKD cells |
American journal of physiology. Renal physiology |
Medium |
18829740
|
| 2020 |
Nuclear cathepsin L proteolytically processes CDP/CUX to generate the p110 isoform, which stably binds to the VEGF-D promoter and promotes VEGF-D transcription, thereby driving angiogenesis in gastric cancer. |
Co-immunoprecipitation, dual-luciferase reporter assay, Western blot, tube formation, HUVEC migration, and CAM assays |
Gastric cancer |
Medium |
32388635
|