| 2021 |
BANP (SMAR1) is a transcription factor that binds the CGCG element (Banp motif) at CpG island promoters in mouse and human genomes. Upon binding to unmethylated CGCG motifs, BANP opens chromatin and phases nucleosomes, activating essential metabolic genes. DNA methylation of the CGCG motif repels BANP binding in vitro and in vivo, epigenetically restricting binding to CpG islands. |
Single-molecule footprinting, interaction proteomics, ChIP-seq, in vitro DNA-binding assays with methylated/unmethylated substrates, chromatin accessibility assays in pluripotent and neuronal cells |
Nature |
High |
34234345
|
| 2023 |
Crystal structure of the BANP BEN domain in apo form and in complex with CGCG-containing DNA revealed that BANP mainly uses electrostatic interactions to bind DNA, with base-specific interactions at TC motifs. The optimal DNA-binding sequence is AAATCTCG. Methylated and unmethylated DNAs are bound with comparable affinity by the isolated BEN domain. |
X-ray crystallography, isothermal titration calorimetry, protein binding microarray, site-directed mutagenesis |
The Journal of biological chemistry |
High |
37086783
|
| 2024 |
Crystal structures of the BANP BEN domain in complex with cognate DNA substrates revealed that oligomerization is required for BANP to select unmethylated CGCG motif-containing DNA substrates, clarifying the mechanism by which BANP functions as a CpG island-binding protein. |
X-ray crystallography of BEN domain–DNA complexes, biochemical oligomerization assays |
Nucleic acids research |
High |
39225042
|
| 2022 |
Zebrafish Banp (ortholog of human BANP) directly regulates transcription of DNA replication fork regulator wrnip1 and chromosome segregation regulators cenpt and ncapg via the Banp motif. Loss of Banp activates DNA replication stress and tp53-dependent DNA damage responses leading to apoptosis, and causes defective chromosome segregation (prolonged M-phase) in developing retina. |
Zebrafish banp mutants and morphants, RNA-seq, ATAC-seq, identification of Banp-motif-containing target genes, epistasis with tp53 |
eLife |
High |
35942692
|
| 2000 |
BANP (originally named SMAR1) was identified as a novel MAR-binding protein that binds the MARbeta scaffold/matrix-associated region located upstream of the TCR beta enhancer. GST-SMAR1 fusion protein binding to MARbeta is competed by MAR-containing DNA from the immunoglobulin kappa locus, demonstrating specificity. The gene maps to mouse chromosome 8 (human 16q24) and produces alternatively spliced transcripts most abundant in thymus. |
EMSA (electrophoretic mobility shift assay), GST pulldown, RT-PCR, chromosomal mapping |
Genomics |
Medium |
10950932
|
| 2000 |
BANP was identified as a BTG3-associated nuclear protein through a yeast two-hybrid screen using BTG3 as bait, and was localized to human chromosome 16q24, a region showing frequent loss of heterozygosity in tumors. |
Yeast two-hybrid screen, chromosomal localization |
Gene |
Low |
10940556
|
| 2003 |
SMAR1 (BANP) physically interacts with and colocalizes with p53, and overexpression of the short isoform SMAR1(S) activates p53-mediated reporter gene expression and its downstream effector p21, causing G2/M cell-cycle arrest and delaying tumor growth in vivo. |
Co-immunoprecipitation, colocalization, reporter gene assays, cell cycle analysis, in vivo tumor growth assay |
International journal of cancer |
Medium |
12494467
|
| 2005 |
SMAR1 (BANP) represses cyclin D1 gene expression by recruiting the SIN3/HDAC1 complex and pocket retinoblastoma proteins to the cyclin D1 promoter MAR element, causing chromatin deacetylation spreading at least 5 kb upstream. The interaction is mediated by SMAR1 domain aa 160-350. |
Co-immunoprecipitation, ChIP, reporter assays, siRNA knockdown |
Molecular and cellular biology |
High |
16166625
|
| 2005 |
The arginine-serine-rich (RS) domain of SMAR1 (BANP) is phosphorylated by protein kinase C family proteins and is the minimal domain responsible for interaction with, activation, and nuclear stabilization of p53. SMAR1 stabilizes p53 by inhibiting MDM2-mediated degradation. Serine 347 of SMAR1 is the PKC phosphorylation site indispensable for its activity. |
Domain deletion/mutagenesis, in vitro phosphorylation assays, co-immunoprecipitation, siRNA knockdown, SMAR1 transgenic mice |
The Journal of biological chemistry |
High |
15701641
|
| 2004 |
SMAR1 and Cux/CDP modulate chromatin structure at the MARbeta region (by DNaseI hypersensitivity) and independently repress TCRbeta enhancer-dependent transcription. SMAR1 and Cux physically interact and colocalize in the perinuclear region; repression is enhanced by their co-expression. The repression domain of SMAR1 is distinct from its MAR-binding domain and contains an NLS and RS-rich domain. |
DNaseI hypersensitivity, reporter assays, Co-immunoprecipitation, colocalization imaging, domain mapping |
Nucleic acids research |
Medium |
15371550
|
| 2009 |
SMAR1 forms a ternary complex with MDM2 and Ser15-phosphorylated p53 in the post-stress recovery phase. This complex recruits HDAC1 to deacetylate p53, causing p53 to bind poorly to target promoters (e.g., p21), switching off the p53 response to allow cell cycle re-entry. SMAR1 knockdown prolongs cell-cycle arrest post-stress. |
Co-immunoprecipitation, ChIP, reporter assays, siRNA knockdown |
Journal of molecular biology |
Medium |
19303885
|
| 2010 |
SMAR1 represses BAX and PUMA promoters by binding to an identical MAR element present in both promoters, independently of p53. On mild DNA damage, SMAR1 selectively represses these pro-apoptotic genes via HDAC1-mediated p53 deacetylation, generating cell cycle arrest instead of apoptosis. On severe DNA damage, SMAR1 is sequestered by enlarged PML nuclear bodies, releasing SMAR1 binding and allowing p53 acetylation and apoptosis. |
ChIP, reporter assays, Co-IP, siRNA knockdown, PML body imaging, SMAR1 mutant analysis |
The EMBO journal |
High |
20075864
|
| 2010 |
SMAR1 binds to the HIV-1 LTR MAR element and recruits the HDAC1-mSin3 corepressor complex, tethering the LTR to the nuclear matrix and silencing HIV transcription. Cellular activation by PMA/TNFα dislodges the corepressor, increases histone acetylation, reduces trimethylation, and enables RNA Pol II recruitment. |
ChIP, reporter assays, corepressor complex Co-IP, nuclear matrix fractionation, virion production assay |
Virology |
Medium |
20153010
|
| 2010 |
SMAR1 directly interacts with and inhibits AKR1a4 enzyme activity in the cytoplasm. Upon stress, ATM kinase triggers nuclear translocation of SMAR1, which dissociates the SMAR1-AKR1a4 complex and elevates AKR1a4 activity for free radical scavenging. |
Co-immunoprecipitation, enzyme activity assay, subcellular fractionation, ATM inhibitor experiments |
The international journal of biochemistry & cell biology |
Medium |
20097305
|
| 2012 |
TCF-4, β-catenin, and SMAR1 form a complex that tethers the HIV LTR at the -143 nt site, repressing basal HIV promoter activity. Deletion/mutation of this site or knockdown of TCF-4/β-catenin increases basal LTR activity ~5-fold but does not affect Tat-mediated transactivation. |
ChIP, luciferase reporter assays, siRNA knockdown, mutant LTR constructs |
Journal of virology |
Medium |
22674979
|
| 2014 |
SMAR1 inhibits EMT in breast cancer cells via two mechanisms: (1) transcriptional repression of Slug by recruiting an SMAR1/HDAC1 complex to the MAR site in the Slug promoter, restoring E-cadherin expression; and (2) blocking E-cadherin-MDM2 interaction, thereby preventing MDM2-mediated ubiquitination and degradation of E-cadherin protein. |
ChIP, Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, migration assay |
The Journal of biological chemistry |
High |
25086032
|
| 2015 |
SMAR1 negatively regulates alternative splicing through HDAC6-mediated deacetylation of Sam68. SMAR1 associates with splicing speckles and snRNAs. ERK1/2-mediated phosphorylation of SMAR1 at Thr345 and Thr360 causes its cytoplasmic translocation, releasing the SMAR1-HDAC6-Sam68 inhibitory complex and allowing Sam68 acetylation and alternative splicing (e.g., CD44 variant exon inclusion). |
Co-immunoprecipitation, nuclear/cytoplasmic fractionation, CLIP, phosphorylation mapping by mutagenesis, ChIP, alternative splicing assays, in vivo metastasis model |
Proceedings of the National Academy of Sciences of the United States of America |
High |
26080397
|
| 2014 |
SMAR1 coordinates HDAC6-mediated deacetylation of Ku70, maintaining Ku70 in a deacetylated state that allows its association with Bax and suppression of Bax mitochondrial translocation (providing radioresistance). Ionizing radiation induces SMAR1 expression and ATM-mediated phosphorylation at Ser370, redistributing SMAR1 to nuclear foci. SMAR1 also facilitates Chk2 phosphorylation to enforce G2/M arrest. |
Co-immunoprecipitation, chromatin fractionation, acetylation assays, siRNA knockdown, phospho-mutant analysis, irradiation experiments |
Cell death & disease |
Medium |
25299772
|
| 2017 |
Cdc20, a substrate receptor of the APC/C ubiquitin ligase complex, binds SMAR1 via its D-box motif and promotes K48-linked polyubiquitylation and proteasomal degradation of SMAR1. shRNA-mediated knockdown of Cdc20 stabilizes SMAR1. Genotoxic stress prevents Cdc20-mediated SMAR1 degradation. |
Co-immunoprecipitation, ubiquitination assay (K48-specific), shRNA knockdown, D-box mutant analysis, proteasome inhibitor experiments |
Cell death & disease |
High |
28617439
|
| 2008 |
SMAR1 binds directly to a MAR site in the IκBα promoter and recruits a corepressor complex to repress IκBα transcription. SMAR1 also inhibits p65 transactivation by producing phosphorylation-deficient NF-κB complexes, downregulating a subset of tumorigenic NF-κB target genes. |
ChIP, reporter assays, Co-immunoprecipitation, NF-κB target gene array |
The Journal of biological chemistry |
Medium |
18981184
|
| 2021 |
SMAR1 regulates PKM alternative splicing by recruiting HDAC6 to deacetylate PTBP1, reducing PTBP1 enrichment on PKM pre-mRNA, thereby suppressing PKM2 isoform expression and inhibiting the Warburg effect in cancer cells. |
Co-immunoprecipitation, CLIP, acetylation assays, qRT-PCR, enzymatic glycolysis assays, in vivo tumor assay |
Cancer & metabolism |
Medium |
33863392
|
| 2015 |
SMAR1 negatively regulates STAT3 expression by binding to the MAR element of the STAT3 promoter, adjacent to IL-6 response elements, favoring Foxp3 expression and regulatory T cell differentiation over Th17 differentiation in the context of inflammatory bowel disease. |
ChIP, T cell-specific conditional SMAR1 knockout mice, colitis models, cytokine assays |
Mucosal immunology |
Medium |
25993445
|
| 2015 |
SMAR1 functions as a negative regulator of Th1 and Th17 differentiation by recruiting the HDAC1-SMRT complex to MAR regions on the T-bet and IL-17 promoters, thereby repressing their transcription and promoting Th2 cell establishment in the context of allergic airway disease. |
ChIP, T cell-specific conditional SMAR1 knockout mice, airway inflammation model, cytokine assays |
Mucosal immunology |
Medium |
25736456
|
| 2018 |
SMAR1 inhibits Wnt/β-catenin signaling by recruiting HDAC5 to the β-catenin promoter, reducing its transcription. SMAR1 is itself degraded via its D-box elements ('RCHL' and 'RQRL') in response to aberrant Wnt3a signaling; substitution mutations in these D-box elements completely abrogate proteasomal degradation. |
ChIP, reporter assays, mutagenesis of D-box elements, isothermal titration calorimetry, in vivo tumor assay |
Oncotarget |
Medium |
29765542
|
| 2007 |
SMAR1 mRNA is stabilized by Prostaglandin A2 (PGA2) through a stem-loop structure in its 5' UTR (the '1-UTR' form). This stabilization leads to increased SMAR1 protein and subsequent downregulation of Cyclin D1. Breast cancer cell lines harbor a variant 5' UTR ('17-UTR') lacking this stem-loop, making SMAR1 mRNA non-responsive to PGA2 stabilization. |
RNA EMSA, 5' UTR deletion/mutation constructs, reporter assays, RT-PCR quantification |
Nucleic acids research |
Medium |
17726044
|
| 2010 |
HSP70 binds to a novel site in the 5' UTR of SMAR1 (the phi1 form) upon PGA2 treatment, stabilizing the wild-type SMAR1 transcript and increasing protein levels, contributing to PGA2-mediated cell cycle arrest. HSP70 cannot bind the phi17 variant 5' UTR present in breast cancer cells. |
RNA pulldown/RIP assays, HSP70 knockdown, mRNA stability assays |
FEBS letters |
Medium |
20153327
|
| 2009 |
TNFα stimulation induces phosphorylation of SMAR1 at Ser-347, promoting its cytoplasmic translocation and releasing its negative regulation of CD40 transcription. Simultaneously, TNFα-induced JAK1-mediated phosphorylation of STAT1 at Tyr-701 enables STAT1 nuclear translocation and CD40 activation via p300 recruitment and histone H3 acetylation. |
Phospho-specific detection, subcellular fractionation, ChIP, reporter assays |
Biochemical and biophysical research communications |
Medium |
20006573
|
| 2024 |
BANP promotes p53 phosphorylation and nuclear retention in vascular endothelial cells exposed to chronic intermittent hypoxia, inducing cellular senescence. BANP overexpression alone was sufficient to induce senescence. |
BANP overexpression in HUVECs, EdU assay, cell cycle analysis, SA-β-gal staining, Western blot for p53/p21, in vivo CIH rat model |
Gerontology |
Low |
38168028
|
| 2024 |
ZNF471 interacts with BANP in renal cell carcinoma cells and suppresses the PI3K/AKT/mTOR signaling pathway to inhibit cancer malignancy. |
Co-immunoprecipitation, signaling pathway analysis, functional cell biology assays |
International journal of biological sciences |
Low |
38169650
|
| 2011 |
SMAR1 inhibits p53 acetylation and p53-dependent apoptosis by repressing p300 expression and by interacting with the p53-p300 transcriptional complex to antagonize p300-p53 interaction, thereby suppressing activation of p53 apoptotic targets and miR-34a. |
Co-immunoprecipitation, reporter assays, siRNA knockdown, Western blot |
The international journal of biochemistry & cell biology |
Medium |
22074660
|
| 2020 |
SMAR1 expression in breast cancer stem cells is repressed by cooperative interaction of pluripotency factors Oct4 and Sox2 with HDAC1 at the SMAR1 promoter. Conversely, SMAR1 suppresses ABCG2 transcription by recruiting HDAC2 to the ABCG2 promoter, sensitizing cancer stem cells to chemotherapy. |
ChIP, Co-immunoprecipitation, reporter assays, shRNA, in vivo tumor model |
Science signaling |
Medium |
33082288
|