| 1989 |
HIVEP1 (HIV-EP1) was identified as a zinc finger protein that specifically binds to the HIV-1 enhancer (NF-κB binding site, GGGACTTTCC). DNase I footprinting with recombinant protein expressed in E. coli demonstrated direct, specific binding to the HIV-1 enhancer sequence. The protein contains two tandem C2H2-type zinc finger sequences required for DNA binding. |
Southwestern cloning, DNase I footprinting with recombinant protein expressed in E. coli |
The Journal of biological chemistry |
High |
2504707
|
| 1991 |
HIVEP1 (HIV-EP1/MBP-1/PRDII-BF1) encodes a ~298-kDa protein with two widely separated zinc finger DNA-binding domains, each of which binds the same κB DNA sequence. The gene was mapped to human chromosome 6p22.3-p24. |
cDNA analysis, chromosomal mapping by in situ hybridization and somatic cell hybrid analysis |
Genomics |
Medium |
2037300
|
| 1992 |
HIVEP1 (PRDII-BF1) produces two protein isoforms via alternative splicing, both of which specifically bind to the HIV NF-κB motif and related enhancer elements in the immunoglobulin κ, class I MHC, and IL-2 receptor genes. When fused to the GAL4 DNA-binding domain, PRDII-BF1-derived proteins did not stimulate basal or Tat-induced HIV gene expression, indicating HIVEP1 does not act as a transcriptional activator of HIV LTR in this context. |
DNA-binding assays, GAL4 fusion cotransfection with HIV LTR-CAT reporter |
Journal of virology |
Medium |
1727488
|
| 1990 |
The α A-CRYBP1 regulatory site (to which HIVEP1/αA-CRYBP1 binds) in the mouse αA-crystallin promoter activated transcription in a mouse lens epithelial cell line in a copy-number- and cell-type-dependent manner; a single copy conferred lens specificity while multiple copies extended expression to non-lens cells including fibroblasts and B cells. |
Transient transfection of thymidine kinase reporter constructs in lens and non-lens cell lines |
Molecular and cellular biology |
Medium |
2247086
|
| 1993 |
Multiple HIVEP1 (αA-CRYBP1) antigenically related proteins of different sizes (50 kDa, 90 kDa, and >200 kDa) interact with the αA-CRYBP1 regulatory sequence, as shown by UV-crosslinking and double-label immunoblotting with a specific antibody. The large isoform (>200 kDa) was detected only in fibroblasts, not in lens cells, suggesting differential processing or alternative splicing generates tissue-specific forms. |
UV-crosslinking of protein-DNA complexes, double-label immunoblotting with specific antibody against αA-CRYBP1 |
Gene |
Medium |
8406008
|
| 1993 |
The DE-1 and αA-CRYBP1 binding sites in the mouse αA-crystallin promoter are functionally redundant for lens-specific expression in transgenic mice; individual site mutations preserved lens activity, but simultaneous mutation or deletion of both sites abolished lens expression entirely. |
Site-directed mutagenesis, stable transformation of lens cells, transgenic mouse CAT reporter assay |
Nucleic acids research |
High |
8332460
|
| 1995 |
Novel zinc-chelating heterocyclic compounds inhibit the DNA-binding activity of HIVEP1 (HIV-EP1) by removing zinc from its C2H2 zinc finger domain, demonstrating that zinc coordination is essential for HIVEP1 DNA-binding activity. Distinct compounds selectively inhibited either HIVEP1 or NF-κB DNA binding without affecting the other, enabling functional discrimination between the two κB-site-binding proteins. |
In vitro DNA-binding inhibition assay, NMR confirmation of zinc chelation |
Journal of medicinal chemistry |
Medium |
7650680
|
| 1996 |
Novel pyridine-aminoalkanethiol zinc chelators inhibit HIVEP1 DNA-binding with IC50 ~4 µM (10-fold more potent than histidine-based inhibitors), and do so by a mechanism distinct from histidine-based chelators, further confirming that zinc coordination in the zinc finger domain is the critical determinant of HIVEP1 DNA-binding activity. |
In vitro DNA-binding inhibition assay with purified HIVEP1 protein |
Journal of medicinal chemistry |
Medium |
8558519
|
| 2009 |
HIVEP1 (via its C-terminal fragment Cirip/CIRIP, which retains the zinc fingers) physically interacts with Cirhin (CIRH1A) in the nuclei of HeLa cells. This interaction upregulates transcription through a canonical NF-κB element. The NAIC-associated R565W mutation in Cirhin weakens this interaction and reduces transactivation of the NF-κB element, establishing a functional Cirhin–HIVEP1 complex in transcriptional regulation. |
Yeast two-hybrid screening, co-immunoprecipitation from nuclear extracts, mammalian cell NF-κB reporter assay |
Experimental cell research |
High |
19732766
|
| 2021 |
HIVEP1 functions as a negative regulator of NF-κB in monocytes/macrophages. In complementary overexpression and gene-deletion experiments, HIVEP1 inhibited NF-κB activity and induction of NF-κB-responsive genes. HIVEP1 was shown to bind promoter regions of NF-κB-responsive genes by ChIP. In LPS-stimulated murine Hivep1-knockout macrophages and HIVEP1-knockdown zebrafish infected with Streptococcus pneumoniae, cytokine production was increased, demonstrating HIVEP1 suppresses proinflammatory responses to bacterial stimuli in vitro and in vivo. |
Overexpression and gene deletion experiments, RNA sequencing, transcription factor binding site analysis, ChIP (promoter binding), murine Hivep1 KO macrophages, HIVEP1-knockdown zebrafish infection model |
Frontiers in immunology |
High |
34804025
|
| 2025 |
HIVEP1 acts as a transcription factor that promotes TH17 cell differentiation and cytokine production by transcriptionally activating ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme of polyamine metabolism. Specific knockout of Hivep1 in IL-17A+ and CD4+ T cells in mice impaired TH17 differentiation and alleviated NASH development, and pharmacological inhibition of ODC1 phenocopied the protective effect. |
scATAC-seq, scRNA-seq, conditional Hivep1 knockout in IL-17A+ and CD4+ T cells, transcriptional target identification (ODC1), pharmacological ODC1 inhibition in vivo |
Science translational medicine |
High |
41124285
|