| 1994 |
B61 (TNFAIP1) was identified as the ligand for the ECK receptor protein-tyrosine kinase; recombinant B61 induces autophosphorylation of ECK in intact cells, and B61 was purified by receptor affinity chromatography using the extracellular domain of ECK. |
Receptor affinity chromatography, surface plasmon resonance, cell-based autophosphorylation assay |
Nature |
High |
8139691
|
| 1995 |
B61 can exist as a cell-surface glycosylphosphatidylinositol (GPI)-linked protein, in addition to its soluble secreted form, and the GPI-linked form is capable of activating the ECK receptor protein-tyrosine kinase. |
PI-PLC treatment, cell-based receptor activation assay, biochemical characterization |
The Journal of biological chemistry |
High |
7890684
|
| 1995 |
B61, acting through the ECK receptor tyrosine kinase, functions as an angiogenic factor in vivo and as a chemoattractant for endothelial cells in vitro; TNF-alpha induces angiogenesis through induction of B61, which then activates ECK in an autocrine/paracrine loop, and an anti-B61 antibody attenuated TNF-alpha-induced but not bFGF-induced angiogenesis. |
B61-immunoglobulin chimera in vivo angiogenesis assay, endothelial cell chemotaxis assay, antibody neutralization |
Science |
High |
7536959
|
| 2009 |
TNFAIP1 directly interacts with RhoB; co-immunoprecipitation and in vitro binding assays confirmed the interaction. RFP-TNFAIP1 partially co-localizes with EGFP-RhoB in endosomes. TNFAIP1 elicits pro-apoptotic activity, and simultaneous expression of RhoB and TNFAIP1 dramatically increases apoptosis in HeLa cells via SAPK/JNK signaling; knockdown of RhoB by siRNA rescued cells from TNFAIP1-induced apoptosis. |
Yeast two-hybrid, co-immunoprecipitation, in vitro binding assay, fluorescence co-localization, siRNA knockdown, JNK inhibitor experiment |
International journal of cancer |
High |
19637314
|
| 2009 |
CK2 (casein kinase 2) phosphorylates TNFAIP1 both in vitro and in vivo; CK2β was identified as a TNFAIP1-interacting partner. Phosphorylation by CK2 facilitates nuclear distribution of TNFAIP1 and enhances its interaction with PCNA. |
Yeast two-hybrid screening, in vitro kinase assay, in vivo phosphorylation assay, subcellular fractionation, co-immunoprecipitation |
Molecular biology reports |
Medium |
19851886
|
| 2012 |
TNFAIP1 interacts with KCTD10, confirmed by yeast two-hybrid, GST pull-down, co-immunoprecipitation, and co-localization. TNFAIP1 overexpression promotes ubiquitin-mediated proteasomal degradation of KCTD10 (reversed by MG132), and both TNFAIP1 and KCTD10 inhibit NF-κB and AP-1 transcriptional activity. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, co-localization, ubiquitin/proteasome assay, reporter assay |
Molecular biology reports |
Medium |
22810651
|
| 2016 |
TNFAIP1 (Bacurd2) acts as an interacting partner to Rnd2 and Rnd3 GTPases in vitro. In utero electroporation experiments in mice show that disruption of Tnfaip1/Bacurd2 expression impairs the long-term positioning of cortical neurons within the postnatal cerebral cortex and alters branching and dendritic spine properties of layer II/III projection neurons. |
In vitro interaction assay, in utero electroporation, immunofluorescence in postnatal mouse brain |
Neural development |
Medium |
26969432
|
| 2020 |
The CRL3BTBD9 E3 ubiquitin ligase complex targets TNFAIP1 for polyubiquitination and proteasomal degradation: Cul3-ROC1 (CRL3) specifically interacts with TNFAIP1 and promotes its degradation, with BTBD9 as the specific substrate adaptor. Downregulation of BTBD9 promotes lung cancer cell migration by upregulating TNFAIP1, and TNFAIP1 deletion abrogated this effect. |
Label-free quantitative proteomics, co-immunoprecipitation, ubiquitination assay, cell migration assay, genetic rescue experiment |
Signal transduction and targeted therapy |
High |
32327643
|
| 2021 |
TNFAIP1 coordinates with Cullin3 to mediate RhoB degradation through the ubiquitin proteasome system in hepatocellular carcinoma cells. Downregulation of TNFAIP1 induces expression of pro-inflammatory cytokines IL-6 and IL-8 in TNFα-stimulated cells through p38/JNK MAPK pathway via blocking RhoB degradation. |
Co-immunoprecipitation, ubiquitin assay, cytokine ELISA, siRNA knockdown, pathway inhibitor experiments |
Frontiers in cell and developmental biology |
Medium |
33553178
|
| 2023 |
TNFAIP1 acts as an E3 ubiquitin ligase that directly binds SNAP25 (via its N-terminal residues 1-96) and mediates K48-linked polyubiquitination of SNAP25 at K69, leading to proteasomal degradation of SNAP25. Neuron-specific knockdown of TNFAIP1 in mice ameliorated postoperative cognitive dysfunction, restored PINK1/Parkin mitophagy, and reduced caspase-3/GSDME pyroptosis; these effects were reversed by SNAP25 co-depletion. |
Co-immunoprecipitation, ubiquitination assay with K48-linkage-specific analysis, domain-mapping, AAV9-hSyn neuronal knockdown in mice, behavioral testing, western blot |
Cell communication and signaling : CCS |
High |
38102610
|
| 2024 |
HECTD2 promotes ubiquitin-mediated degradation of EHMT2, leading to upregulation of TNFAIP1 transcription (ChIP confirmed TNFAIP1 as a direct target of EHMT2). High TNFAIP1 expression promotes inflammatory response in renal cell carcinoma cells via the p38/JNK pathway; p38/JNK inhibitors attenuated the effect of TNFAIP1 overexpression. |
Co-immunoprecipitation, western blot, ChIP assay, qRT-PCR, ELISA, pathway inhibitor experiments |
In vivo (Athens, Greece) |
Medium |
38688591
|
| 2023 |
TNFAIP1 interacts with CK2β and promotes its degradation by ubiquitination (confirmed by co-immunoprecipitation and western blotting); miR-93 negatively regulates TNFAIP1 expression (dual-luciferase reporter), and miR-93 overexpression prevented DEHP-induced neurotoxicity by downregulating TNFAIP1 and then activating CK2/Akt/CREB pathway. |
Co-immunoprecipitation, western blot, ubiquitination assay, dual-luciferase reporter assay, miRNA overexpression in cells and mice |
Food and chemical toxicology |
Medium |
37302538
|
| 2024 |
Knockdown of TNFAIP1 in THP-1 macrophages enhanced lncRNA LEENE expression, promoted direct interaction of LEENE with FoxO1 protein (verified by RNA immunoprecipitation and RNA pull-down), stimulated FoxO1 proteasomal degradation, induced ABCA1 transcription, and suppressed lipid accumulation; in apoE-/- mice, TNFAIP1 knockdown upregulated ABCA1, improved lipid profiles, and attenuated atherosclerotic lesion area. |
Lentiviral knockdown, RNA immunoprecipitation, RNA pull-down, western blot, qRT-PCR, Oil Red O staining, HPLC, in vivo mouse model |
Journal of physiology and biochemistry |
Medium |
38878215
|
| 2009 |
The TNFAIP1 gene promoter contains a functional Sp1-binding site within the core promoter region; gel EMSA, site-directed mutagenesis, and ChIP confirmed Sp1 binding in vivo and in vitro, and Sp1 overexpression enhanced TNFAIP1 promoter activity. |
Deletion mutation analysis, gel electrophoretic mobility shift assay (EMSA), site-directed mutagenesis, chromatin immunoprecipitation (ChIP), reporter assay |
Molecular biology reports |
Medium |
19593659
|
| 2014 |
Estrogen receptor β (ERβ) binds to the Tnfaip1 promoter and upregulates Tnfaip1 expression in mouse hippocampal cells; ovariectomy increased Tnfaip1 expression in hippocampus, and primary hippocampal cell culture experiments with estrogen and ER antagonists confirmed regulation of Tnfaip1 levels by estrogen. |
Reporter assay, promoter binding site identification, in vivo ovariectomy model, primary hippocampal cell culture, immunostaining |
International journal of molecular medicine |
Medium |
24737445
|
| 2023 |
In zebrafish, CRISPR/Cas9-mediated knockout of tnfaip1 caused developmental delays, microcephaly and microphthalmia, and decreased expression of neuronal marker genes (tuba1b, neurod1, ccnd1), establishing a role for tnfaip1 in early embryonic neural development. |
CRISPR/Cas9 knockout in zebrafish, whole mount in situ hybridization, qRT-PCR, transcriptome sequencing |
Genes |
Medium |
37239365
|
| 2026 |
TNFAIP1 directly interacts with PXR (pregnane X receptor), confirmed by co-immunoprecipitation. TNFAIP1 positively regulates the PXR/CYP3A4 pathway; TNFAIP1 knockout decreased CYP3A4 expression and impaired PXR agonist (rifampicin)-induced CYP3A4 upregulation in HCC cells. In vivo, Tnfaip1 overexpression upregulated Pxr/Cyp3a11 and inhibited tumor growth. |
Co-immunoprecipitation, western blot, qRT-PCR, TNFAIP1 knockout, pharmacological PXR activation, in vivo tumor xenograft |
American journal of cancer research |
Medium |
42004057
|
| 2016 |
TNFAIP1 knockdown inhibits growth and induces apoptosis in osteosarcoma cells, associated with downregulation of p65 NF-κB, PCNA, and MMP-2 and upregulation of caspase-3, placing TNFAIP1 upstream of NF-κB in osteosarcoma cell survival signaling. |
Lentiviral siRNA knockdown, MTT assay, Transwell invasion assay, flow cytometry, western blot for NF-κB/PCNA/MMP-2/caspase-3 |
Oncology reports |
Low |
24969828
|
| 2020 |
TNFAIP1 overexpression inhibits levels of phosphorylated Akt and CREB and anti-apoptotic Bcl-2, contributing to Aβ-induced neurotoxicity; TNFAIP1 knockdown reversed these effects and reduced cleaved caspase-3, placing TNFAIP1 upstream of the Akt/CREB/Bcl-2 apoptotic axis. |
siRNA knockdown, overexpression, western blot for p-Akt, p-CREB, Bcl-2, cleaved caspase-3 in N2a cells |
BMC neuroscience |
Low |
27430312
|
| 2020 |
TNFAIP1 is upregulated in APP/PS1 mouse neurons; Aβ increases binding of TNFAIP1 to RhoB (co-immunoprecipitation), and RhoB knockdown attenuates TNFAIP1-induced apoptosis in SH-SY5Y cells, confirming that TNFAIP1-RhoB interaction mediates apoptosis in an AD model. |
Co-immunoprecipitation, siRNA knockdown, western blot, flow cytometry, APP/PS1 transgenic mice immunostaining |
Journal of molecular neuroscience |
Medium |
33159672
|