| 1998 |
PREP1 forms a stable heterodimer with PBX proteins independent of DNA binding, requiring sequences in the N-terminal portions of both proteins (HR1/HR2 domains). The PREP1-PBX interaction is essential for DNA-binding activity, and PREP1 enhances the ability of the HOXB1-PBX1 complex to activate transcription cooperatively, including formation of a ternary PREP1-PBX1-HOXB1 complex on a HOXB1-responsive target in vitro. |
Co-immunoprecipitation, in vitro protein-protein interaction assays, EMSA, transient transfection transcriptional assays, mutagenesis of homeodomain and N-terminal interaction surfaces |
The EMBO journal |
High |
9482740
|
| 1998 |
PREP1 was cloned as a subunit of the UEF3 complex (urokinase plasminogen activator enhancer factor 3). PREP1 is a TALE-class homeodomain protein that forms a stable complex with PBX proteins in solution independent of DNA, and the heterodimer binds the TGACAG motif in the uPA promoter with high affinity. The other UEF3 subunit was identified as a PBX family member. |
cDNA cloning, EMSA, co-immunoprecipitation, in vitro binding assays |
The EMBO journal |
High |
9482739
|
| 1997 |
PKNOX1 (PREP1) dimerizes with PBX1 on the TGATTGAC motif and binds DNA cooperatively. The PKNOX1/MEIS1-interaction domain in PBX1 resides in a conserved N-terminal PBX domain deleted in the leukemic oncoprotein E2a-PBX1; consequently, PKNOX1 and MEIS1 fail to dimerize significantly with E2a-PBX1. |
EMSA, GST pull-down, nuclear extract binding assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9405651
|
| 1999 |
PREP1 is cytoplasmic and requires association with PBX/EXD for nuclear localization. Coexpression of EXD/PBX with PREP1/HTH causes nuclear localization of their heterodimers in both mammalian fibroblasts and Drosophila Schneider cells. Heterodimerization with PBX induces nuclear translocation of PREP1 by blocking nuclear export of PBX. |
Immunofluorescence microscopy, subcellular fractionation, co-expression experiments in multiple cell contexts |
Genes & development |
High |
10215622
|
| 1999 |
PREP1-PBX heterodimers bind the UE-A element of the somatostatin promoter cooperatively (neither protein alone can bind), and both PBX1 and PREP1 are required for transcriptional activation from this element. In the context of the intact somatostatin mini-enhancer, PREP1-PBX1 cooperates with the pancreatic homeodomain factor PDX1 to produce drastic transcriptional activation. |
EMSA with recombinant proteins, transient transfection reporter assays, co-expression experiments |
The Journal of biological chemistry |
High |
9933599
|
| 2000 |
PREP1-PBX complexes bind Pbx-Meinox (PM) sites in the Hoxb2 r4 enhancer, and the PM site is essential in vivo for r4-restricted expression. Both PM and PH (Pbx-Hox) sites are required for formation and binding of a ternary HOXB1-PBX1a-PREP1 complex in vitro. A similar ternary complex forms in nuclear extracts from retinoic acid-induced P19 cells, containing PREP1 (or MEIS1), PBX, and HOXB1. |
EMSA, transgenic mouse enhancer assays, nuclear extract binding assays, site-directed mutagenesis of enhancer elements |
Development (Cambridge, England) |
High |
10654609
|
| 1999 |
PREP1 is present in mouse embryos from at least E9.5, is ubiquitously nuclear in embryonic tissues (E7.5–17.5), and forms tissue-specific DNA-binding complexes with different PBX family members depending on cell type. PREP1 super-activates the PBX-HOXB1 autoregulated Hoxb-1 promoter, and all three proteins (PREP1, PBX, HOXB1) are co-localized in rhombomere 4 in vivo. |
Co-immunoprecipitation, EMSA, immunohistochemistry, Northern blot, in situ hybridization |
Mechanisms of development |
High |
10381567
|
| 1999 |
PBX-MEIS1/PREP1 heterodimers cooperate with myogenic bHLH proteins (MyoD, myogenin, Mrf-4, Myf-5) for DNA binding. A conserved tryptophan motif N-terminal to the DNA-binding domain of each myogenic bHLH protein is required for cooperative DNA binding with PBX-MEIS1/PREP1. MyoD requires this tryptophan motif to evoke chromatin remodeling at the Myogenin promoter. |
EMSA, mutagenesis, chromatin remodeling assays, transcriptional reporter assays |
Nucleic acids research |
High |
10471746
|
| 2000 |
PREP1-PBX heterodimers bind the glucagon gene promoter (domain B of the G3 enhancer and the cAMP response element and G5 element) and restrict transcription in non-glucagon-producing cells. Coexpression of Pbx1a/1b-Prep1 inhibited the glucagon promoter activated by Pax6 in non-glucagon-producing cells, but had no effect in glucagon-producing islet cells. |
EMSA with specific antiserum and in vitro translated proteins, transient transfection reporter assays |
The Journal of biological chemistry |
Medium |
10869353
|
| 2003 |
PREP1 overexpression increases PBX-2 protein levels by preventing its proteasomal degradation. Dimerization with PREP1 stabilizes PBX-2 protein against cycloheximide-induced decay; the proteasome inhibitor MG132 prevents PBX-2 decay in control cells, indicating PBX-2 is normally degraded by the proteasome and PREP1 binding protects it. |
Cycloheximide chase, proteasome inhibitor (MG132) treatment, Western blot, EMSA, stable transfection |
The Journal of biological chemistry |
High |
12871956
|
| 2004 |
PREP1 binds the FSHβ promoter in a complex with SMAD4 and PBX1 at the -134 activin response element; PBX1 and PREP1 interact physically with SMAD2 and SMAD3 as shown by GST pull-down. Pbx1 and Prep1 bind the mouse FSHβ gene in vivo, and mutation of the -134 site abrogates activin responsiveness. |
EMSA, GST interaction assays, transient transfection, chromatin immunoprecipitation (in vivo binding) |
Molecular endocrinology (Baltimore, Md.) |
High |
14764653
|
| 2005 |
PREP1-PBX1 (PM) binding sites in the Hoxb1 autoregulatory enhancer include three sites (PM1, PM2, and R2/PM3). PM1 and PM2 cooperate to modulate in vivo regulatory activity. R2/PM3 has high binding affinity for PREP1-PBX1 dimers and, in combination with PM1 and R3, inhibits ternary PREP1-PBX1-HOXB1 complex formation in vitro and restricts reporter expression in transgenic embryos. |
EMSA, site-directed mutagenesis, transgenic chicken and mouse embryo reporter assays |
Molecular and cellular biology |
High |
16166636
|
| 2006 |
PREP1 deficiency in hypomorphic Prep1(i/i) mice causes an overall decrease in protein levels of MEIS1, PBX1, and PBX2, strongly reducing total PREP1/MEIS-PBX DNA-binding activity. PREP1 acts upstream of a PBX-MEIS network. The levels of cMyb and Pax6 are significantly decreased in fetal liver and retina of Prep1(i/i) embryos, correlating with hematopoietic and eye phenotypes. |
Western blot, EMSA, immunohistochemistry, hypomorphic mouse model |
Molecular and cellular biology |
High |
16847320
|
| 2006 |
The fetal adrenal enhancer (FAdE) in intron 4 of Ad4BP/SF-1 contains binding sites for PBX-PREP1, PBX-HOX, and Ad4BP/SF-1. PBX/PREP1 and PBX/HOX sites initiate transcription prior to the establishment of the Ad4BP/SF-1 autoregulatory loop during fetal adrenal development. |
Transgenic mouse assays, site-directed mutagenesis of enhancer elements, EMSA |
Molecular and cellular biology |
Medium |
16705164
|
| 2007 |
p160 Myb-binding protein (p160) is a novel PREP1-interacting protein that competes with PBX1 for PREP1 binding in vitro. The N-terminal truncated form p67 binds the sequence 63-LFPLL-67 in the HR1 domain of PREP1; mutation of L63 and L66 impairs binding to both p160/p67 and PBX1. p160 inhibits PREP1-dependent HoxB2 expression. |
Co-immunoprecipitation, in vitro competition assay, site-directed mutagenesis, immunofluorescence colocalization, RT-PCR |
Molecular and cellular biology |
High |
17875935
|
| 2007 |
Tandem affinity purification of PREP1 from nuclear and cytoplasmic fractions identified its interactome, including PBX1b, PBX2, p160 Myb-binding protein (p160), beta-actin, and NMMHCIIA as co-purifying partners. |
Tandem affinity purification (TAP), mass spectrometry |
Proteomics |
Medium |
17623278
|
| 2007 |
IL-10 production by macrophages in response to apoptotic cells is regulated at transcription via the apoptotic-cell-response element (ACRE) in the human IL10 promoter; PREP1 (Pbx-regulating protein 1) and PBX1b bind ACRE and mediate transcriptional activation of IL-10 in response to apoptotic cells in a p38 MAPK-dependent manner. |
Reporter assay (ACRE mapping), EMSA, ChIP, gene knockdown, p38 inhibitor treatment |
Immunity |
High |
18093541
|
| 2008 |
PREP1 directly controls the intrinsic apoptotic pathway by regulating Bcl-x gene expression. Prep1(i/i) MEFs have decreased Bcl-X(L) mRNA and protein. Chromatin immunoprecipitation and transient transfection identified the Bcl-x promoter as a direct transcriptional target of PREP1. Overexpression of Bcl-x rescues the apoptotic defect of Prep1(i/i) MEFs. |
ChIP, transient transfection reporter assay, Western blot, annexin V assay, caspase activity assay, Bcl-x overexpression rescue |
Molecular and cellular biology |
High |
19103748
|
| 2008 |
PREP1 deficiency in skeletal muscle increases insulin sensitivity through a p160-GLUT4 pathway. Reduced Prep1 decreases p160 levels, leading to increased PGC-1α and GLUT4 expression. PREP1 controls the stability of the p160 protein. Overexpression of Prep1 or p160 (but not PBX1) reduces GLUT4 and insulin sensitivity; in vivo delivery of p160 cDNA reverses the molecular phenotype of Prep1(i/i) muscle. |
Hypomorphic mouse model, L6 cell overexpression/knockdown, Western blot, glucose uptake assay, in vivo muscle cDNA delivery |
Molecular and cellular biology |
High |
18644868
|
| 2009 |
Cytoplasmic PREP1 in mouse oocytes interacts with 4EHP (eukaryotic translation initiation factor 4E homolog protein) to repress translation of Hoxb4 mRNA. PREP1 binds the Hoxb4 3'UTR (RNA EMSA), inhibits Hoxb4 mRNA translation >95% in vitro in the presence of 4EHP, and a functional 4EHP-binding motif in PREP1 was identified by mutagenesis. Prep1(i/i) oocytes show oocyte growth failure and increased Hoxb4 protein. |
Confocal microscopy, co-immunoprecipitation, GST pull-down, mutagenesis of 4EHP-binding motif, RNA EMSA, in vitro translation assay, immunohistochemistry |
PloS one |
High |
19365557
|
| 2010 |
PREP1 transcriptionally activates the SHP1 tyrosine phosphatase gene via a promoter element between -2113 and -1778. Both PREP1 and PBX1 bind the SHP1 promoter in vivo and cooperatively induce luciferase activity 30-fold. This leads to attenuation of insulin receptor/IRS1/2 phosphorylation and reduced glycogen storage in liver. Antisense silencing of SHP1 (but not SYP) rescues insulin-dependent IR phosphorylation in PREP1-overexpressing cells. |
ChIP, luciferase reporter assay, Western blot, euglycemic hyperinsulinemic clamp, antisense knockdown, HepG2 overexpression |
Diabetes |
High |
20864515
|
| 2010 |
Prep1 is required for genomic stability. Prep1(i/i) fetal liver cells and MEFs exhibit increased basal DNA damage and chromosomal aberrations/aneuploidy. Acute PREP1 knockdown by siRNA in human fibroblasts induces DNA damage response and increases heterochromatin-associated histone methylation with decreased satellite DNA transcription. Ectopic PREP1 expression rescues DNA damage and heterochromatin methylation. PREP1 deficiency facilitates immortalization and H-Ras(V12)-dependent transformation, partially rescued by Prep1 restoration. |
γH2AX immunofluorescence, cytogenetic analysis, siRNA knockdown, ChIP, satellite DNA transcription assay, transformation assay, rescue experiment |
Proceedings of the National Academy of Sciences of the United States of America |
High |
21715654
|
| 2010 |
Absence of Prep1 in null embryos causes p53-dependent apoptosis of epiblast cells. The embryonic lethality of Prep1(-/-) embryos is partially rescued in a p53(-/-) background but not in a p16(-/-) background, placing PREP1 upstream of p53-dependent apoptosis. Atm downregulation exacerbates the Prep1(-/-) phenotype, suggesting DNA damage as the cause of apoptosis. |
Genetic epistasis (Prep1(-/-)/p53(-/-) double mutants), TUNEL staining, cleaved caspase 3 immunostaining, immunohistochemistry |
Development (Cambridge, England) |
High |
20826531
|
| 2010 |
Excess PREP1 increases sensitivity of cells to genotoxic stress via p53. PREP1 overexpression induces p53, and p53 depletion reverts the apoptotic phenotype of PREP1-overexpressing cells. p53 is identified as a direct transcriptional target of PREP1. PREP1 overexpression also increases anti-apoptotic Bcl-X(L) levels, but pro-apoptotic p53 induction dominates. |
Apoptosis assays (genotoxic stress), p53 siRNA rescue, Western blot, transient transfection reporter assay (implied by 'direct target') |
Nucleic acids research |
Medium |
20110257
|
| 2011 |
PREP1 deficiency results in premature cycling and exhaustion of fetal hematopoietic stem cells (HSCs) through induction of interferon signaling (Stat1-Sca1 IFN-dependent pathway). Prep1 controls the self-renewal ability of FL HSCs, as shown by serial transplantation experiments. |
Hypomorphic mouse model, serial transplantation, flow cytometry, gene expression analysis |
PloS one |
Medium |
25233378
|
| 2013 |
PREP1 regulates mitochondrial oxidative phosphorylation components in skeletal muscle through direct and indirect mechanisms. Muscle-specific ablation of Prep1 increases expression of respiratory chain subunits and mitochondrial enzyme activity. PREP1 stabilizes p160 Mybbp1a, a known inhibitor of PGC-1α activity; Prep1 ablation reduces p160, elevating PGC-1α. ChIP-seq identifies direct PREP1 binding sites in genes encoding mitochondrial components (e.g., Ndufs2). |
Muscle-specific conditional knockout, electron microscopy, treadmill exercise testing, Western blot, ChIP-seq |
Molecular and cellular biology |
High |
24216763
|
| 2013 |
PREP1/PBX1 complex transcriptionally activates the SHIP2 (Inppl1) promoter, and the PREP1-HR mutant (unable to bind PBX1) has no effect on Ship2, demonstrating that PREP1-PBX1 dimerization is required for this transcriptional activation. PREP1 deficiency reduces SHIP2, leading to increased PKCζ/LKB1/AMPK/ACC phosphorylation and reduced hepatic lipogenesis. |
ChIP, luciferase reporter assay, PBX1-binding mutant (HR mutant), Western blot, hypomorphic mouse model |
Diabetologia |
High |
24052111
|
| 2014 |
PREP1 and MEIS1 compete for PBX1 binding in mouse embryonic fibroblasts. PREP1 posttranslationally controls MEIS1 levels by decreasing its stability through sequestering PBX1. MEIS1 alone transforms Prep1-deficient fibroblasts; PREP1 overexpression inhibits MEIS1 tumorigenicity. PREP1 also modifies the DNA binding landscape of MEIS1 and prevents MEIS1 interaction with DDX3X and DDX5. |
Co-immunoprecipitation, protein stability assays, transformation assay, transcriptional profiling, MEF genetic model |
Proceedings of the National Academy of Sciences of the United States of America |
High |
24578510
|
| 2014 |
PREP1 is a novel EMT inducer and prometastatic transcription factor in non-small cell lung cancer. PREP1 overexpression triggers EMT, and PREP1 down-regulation inhibits TGF-β-induced EMT. Mechanistically, PREP1 induces SMAD3 nuclear translocation through transactivation of a regulatory element in the SMAD3 first intron. PREP1 also stabilizes and accumulates PBX1 and induces FRA-1 expression; both FRA-1 and PBX1 are required for PREP1-induced mesenchymal changes. |
Overexpression/knockdown, reporter assay (SMAD3 intron element), Western blot, immunofluorescence (SMAD3 localization), lung colonization assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
25157139
|
| 2015 |
In embryonic stem cells, PREP1 binds ~2,000 novel genomic sites compared to embryo trunk, including a higher proportion of enhancers. RNA-seq identifies ~1800 genes down-regulated in Prep1(-/-) ES cells, including essential components of Wnt and Fgf pathways. Prep1(-/-) ES cells show deficient embryoid body formation and differentiation, rescued by re-expression of PREP1. |
ChIP-seq, RNA-seq, embryoid body differentiation assay, Prep1 knockout ES cells, rescue experiment |
PloS one |
High |
25875616
|
| 2015 |
PREP1 and PBX1 homeodomains (HDs) bind DNA cooperatively. The kinetics of individual PREP1 and PBX1 HDs and their combination show cooperative DNA binding. A novel PREP1 motif flanking the HD at the C-terminus is required for cooperativity. |
NMR spectroscopy, biophysical characterization of recombinant PREP1 HD, DNA binding kinetics |
PloS one |
High |
25856340
|
| 2015 |
High glucose exposure increases NF-κB p65 binding and recruitment of SET7 histone methyltransferase and p300 acetyltransferase to the 5' region of Prep1, leading to enhanced H3K4 methylation and H3K9/14 acetylation and increased Prep1 transcription. Prep1-induced recruitment of MEF2/HDAC5 repressor complex at the Glut4 promoter represses Glut4 expression. |
Chromatin immunoprecipitation (ChIP), Western blot, L6 cell model, streptozotocin diabetic mouse model |
Diabetologia |
High |
26453063
|
| 2017 |
NMR spectroscopy of the PREP1 homeodomain shows that residues flanking the HD participate in DNA binding. Isolated PREP1 and PBX1 HDs bind DNA cooperatively, and a novel PREP1 motif C-terminal to the HD is required for cooperativity with PBX1. |
NMR spectroscopy, surface plasmon resonance/kinetic binding assays, mutagenesis |
Scientific reports |
High |
28094776
|
| 2017 |
The synthetic PREP1(54-72) peptide mimicking the PREP1 region involved in interaction with p160 disrupts the PREP1-p160 interaction in vitro (IC50 = 0.20 μM) and restores insulin signaling impaired by ceramide in L6 skeletal muscle cells. The PREP1-p160 interaction is induced by ceramide treatment. |
In vitro binding competition assay (IC50 determination), co-immunoprecipitation, insulin signaling Western blot, glucose uptake assay, glycogen assay |
Oncotarget |
High |
29069751
|
| 2017 |
PREP1 down-regulation in mesenchymal stromal cells and 3T3-L1 preadipocytes increases adipogenic differentiation. PREP1 restricts DNA binding of C/EBPβ to adipogenic enhancers without affecting C/EBPβ expression or activation, thereby suppressing adipogenesis. |
Prep1 siRNA knockdown, adipogenic differentiation assay, ChIP (C/EBPβ binding), ex vivo bone marrow-derived MSC |
Scientific reports |
Medium |
29138456
|
| 2018 |
PREP1 depletion affects DNA replication timing of middle-to-late-replicating DNA. PREP1 down-regulation increases replication rate, number of simultaneously firing origins, and asymmetry of DNA replication, leading to DNA damage. Genome-wide Repli-seq shows 25% of genome (LADs, LRRs, TTRs) replicates earlier upon PREP1 depletion. PREP1 down-regulation also decreases Lamin B1 levels, suggesting DNA release from the nuclear lamina. |
DNA combing, Repli-seq (genome-wide replication timing), Western blot (Lamin B1), DNA damage assays |
Scientific reports |
High |
29453404
|
| 2018 |
PKnox1/PREP1 is required in a germ cell-intrinsic manner for adult spermatogenesis. Tamoxifen-induced or germ cell-specific PKnox1 loss causes arrest at the c-Kit+ spermatogonia stage with loss of meiotic spermatocytes and compromised c-Kit+ spermatogonia differentiation. |
Conditional/inducible knockout (tamoxifen-Cre, germ cell-specific Cre), immunohistochemistry, flow cytometry |
PloS one |
High |
29293683
|
| 2018 |
PREP1 regulates angiogenesis through the p160/PGC-1α pathway. PREP1 overexpression in mouse aortic endothelial cells increases p160 binding and levels (~4-fold) and reduces PGC-1α (~70%), stimulating angiogenic migration, proliferation, and tube formation. The PREP1(54-72) peptide blocking PREP1-p160 interaction reverts the proangiogenic effects. PREP1 levels increase during bFGF-mediated endothelial colony activation. |
Endothelial cell overexpression, PREP1(54-72) peptide inhibition, migration/proliferation/tube formation assays, Western blot, co-immunoprecipitation, hypomorphic mouse Matrigel plug assay |
FASEB journal |
High |
31618597
|
| 2018 |
PREP1 deficiency reduces olfactory bulb development and impairs BDNF-TrkB signaling: Prep1(i/+) mice show reduced TrkB receptor levels and decreased BDNF-induced ERK1/2 activation. Overexpression of Prep1 in N2A neuronal cells increases TrkB expression levels, BDNF-induced ERK phosphorylation, and cell viability. |
Immunohistochemistry, cytochrome C oxidase activity, Western blot, overexpression in N2A cells, olfactory perception behavioral test |
Molecular neurobiology |
Medium |
29349576
|
| 2018 |
PREP1 and p160 domains interact with a KD of approximately 0.3–1 μM. Both PREP1 (residues 45–155) and p160 (residues 20–160) form folded, monomeric, predominantly alpha-helical domains with unusually high thermal stability. |
Recombinant protein expression, CD spectroscopy, thermal stability assay, binding affinity measurement (KD determination) |
Molecular biotechnology |
Medium |
26979610
|
| 2018 |
SP2 transcription factor forms a complex with PREP1-PBX1 and NF-Y at composite genomic motifs where TALE and NF-Y recognition sequences are separated by 11 bp. SP2 potentiates binding of PBX1:PREP1 and NF-Y to co-occupied regulatory elements; reciprocally, PBX1:PREP1 together with NF-Y recruits SP2 to these sites. |
ChIP-exo sequencing, co-immunoprecipitation, ChIP, motif analysis in MEFs |
The Journal of biological chemistry |
High |
30337366
|
| 2022 |
PREP1 (PKNOX1) regulates nuclear stiffness, expression of LINC complex proteins, and YAP-TAZ mechanotransduction. PREP1 depletion upsets nuclear membrane protein stoichiometry, renders nuclei soft, leads to fortified actomyosin networks with larger focal adhesions and greater traction forces, but impairs YAP-TAZ nuclear translocation. |
PREP1 knockdown, atomic force microscopy (nuclear stiffness), traction force microscopy, YAP-TAZ immunofluorescence, Western blot of LINC complex proteins |
Communications biology |
Medium |
35550602
|
| 2023 |
PKNOX1 acts as a transcription factor for the DHH (desert hedgehog) gene, directly binding the DHH promoter and promoting its expression, thereby activating Hedgehog signaling in stomach adenocarcinoma. ANKRD49 physically interacts with PKNOX1 (co-IP) and uses PKNOX1-mediated transcription of TGF-β1 to activate SMAD signaling and promote EMT. |
Dual-luciferase reporter assay (DHH promoter), ChIP (PKNOX1 binding to TGF-β1 promoter), co-immunoprecipitation (ANKRD49-PKNOX1), Western blot, knockdown experiments |
Cancer cell international |
Medium |
41821002
|
| 2003 |
PBX1 and PREP1 bind the PBX consensus element (PCE, TGATTGAC) in the long terminal repeat of Moloney murine leukemia virus (MLV), confirmed by gel shift assay. Overexpression of PBX1 and PREP1 together enhances MLV transcription, and mutations in the PCE completely inhibit viral transcription. |
EMSA (gel shift), overexpression, site-directed mutagenesis of PCE, transcriptional reporter assay |
Molecular and cellular biology |
Medium |
12529389
|
| 2002 |
PBX2-PREP1 heterodimer binds to the Pbx site in the UGT2B17 promoter and interferes with HNF1α binding to the adjacent HNF1 site, resulting in down-regulation of HNF1α-mediated activation of the UGT2B17 promoter. |
EMSA, GST interaction assays, transient transfection reporter assays |
Molecular pharmacology |
Medium |
12065766
|
| 2008 |
PREP1/PBX2 complex preferentially binds the -2578 G allele in the CCL2 promoter (created by the -2578 G polymorphism) and suppresses basal CCL2 promoter activity compared to the ancestral A allele in astrocytes. |
EMSA, transient transfection reporter assay, supershift with specific antibodies |
Genes and immunity |
Medium |
18480829
|
| 2003 |
PKNOX1 (PREP1) specifically binds the Pbx/POU binding site of the FABP7 promoter in vitro, and overexpression of PKNOX1 in neuroblastoma cells trans-activates the FABP7 promoter. |
EMSA (in vitro binding), transient transfection reporter assay |
Nucleic acids research |
Low |
12771203
|
| 2011 |
The MEIS1 C-terminal transactivating domain, when fused to full-length PKNOX1, confers oncogenic activity: the chimeric PKNOX1-MC protein accelerates onset of HOXA9-induced leukemia in a mouse bone marrow transduction/transplantation model. The absence of a transactivating domain in native PKNOX1 accounts for its lack of pro-leukemic activity despite similar DNA-binding properties. |
Bone marrow transduction/transplantation leukemia model, gene expression profiling, chimeric protein construction |
Blood |
High |
21900201
|
| 2016 |
miR-17-5p and miR-19a-3p of the miR-17~92 cluster target PKNOX1, validated as a direct target. PKNOX1 competitively inhibits MEIS1-PBX complex formation; PKNOX1 acts antagonistically to leukemia in an MLL-AF9 murine model. |
miRNA target validation (luciferase reporter), co-immunoprecipitation (competitive PBX binding), murine MLL-AF9 leukemia model, knockdown studies |
Leukemia research |
Medium |
27123834
|
| 2019 |
PREP1 forms complexes with SNAIL2 in mammary stem/progenitor cells and protects SNAIL2 from proteasome-mediated degradation. Prep1-deficient mammary progenitor cells show reduced Snail2, Snail1, and vimentin expression, reduced mammosphere formation and branching in 3D assay, and increased TP53-dependent apoptosis. |
Co-immunoprecipitation (PREP1-SNAIL2 complex), proteasome inhibitor rescue, mammosphere assay, 3D branching assay, Western blot, conditional KO mouse model |
The International journal of developmental biology |
Medium |
30604852
|