| 2010 |
LRRFIP1 functions as a cytosolic nucleic acid sensor that binds exogenous double-stranded RNA and double-stranded DNA, then interacts with β-catenin to promote its activation; activated β-catenin binds the C-terminal domain of IRF3 and recruits the acetyltransferase p300 to the IFN-β enhanceosome, thereby increasing IFN-β production in macrophages in response to VSV and Listeria monocytogenes. |
Co-immunoprecipitation, knockdown (siRNA/shRNA), overexpression, reporter assays, nucleic acid binding assays in macrophages |
Nature immunology |
High |
20453844
|
| 2003 |
GCF2/LRRFIP1 is a transcriptional repressor of the EGFR promoter; deletion mutagenesis mapped the DNA-binding and repression domain to amino acids 429–528, and GCF2 also suppresses AP2-mediated activation of the EGFR promoter. GCF2 protein was detected in both nuclear and cytoplasmic compartments. |
Deletion mutagenesis, promoter-reporter assays, subcellular fractionation/Western blot, Northern blot |
Biochimica et biophysica acta |
Medium |
14522076
|
| 2005 |
GCF2/LRRFIP1 binds the TNF-α −308 promoter site and acts as a transcriptional repressor; it occupies the −308 site in cells that do not produce TNF-α, whereas Ets-1 binds this site in TNF-α-competent cells. Active transcription is additionally accompanied by NF-κB and c-Jun binding to the proximal promoter. |
Affinity purification of binding proteins, chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), surface plasmon resonance |
Molecular and cellular biology |
High |
16199883
|
| 2010 |
In human platelets, LRRFIP1 functions as a component of the platelet cytoskeleton, where it interacts with the actin-remodeling proteins Flightless-1 and Drebrin, as identified by proteomic analysis of LRRFIP1-interacting proteins. Morpholino-based silencing in zebrafish demonstrated a significant positive regulatory role for lrrfip1 in thrombus formation. |
Proteomic co-immunoprecipitation (LRRFIP1 interactome), morpholino knockdown in Danio rerio, correlation analysis of platelet RNA expression |
Blood |
Medium |
20833976
|
| 2010 |
LRRFIP1 is phosphorylated on serine residues, and this phosphorylation is altered by poly I:C and nicotine stimulation. Upon dsRNA stimulation, LRRFIP1 colocalizes with labeled dsRNA in monocyte lysosomal structures, whereas it does not colocalize with lysosomes lacking dsRNA. |
Western blot for serine phosphorylation, immunofluorescence colocalization with labeled dsRNA and lysosomal markers |
Biochemistry and cell biology |
Medium |
21102652
|
| 2012 |
GCF2/LRRFIP1 acts upstream of the small GTPase RhoA as a transcriptional repressor; overexpression of GCF2 results in loss of RhoA expression, disruption of the actin/filamin network, internalization of membrane transporter MRP1 from the cell surface into cytoplasm, increased doxorubicin accumulation, and increased cisplatin resistance. siRNA knockdown of GCF2 in cisplatin-resistant cells reactivated RhoA, restored actin microfilament structure, and relocated MRP1 to the cell surface. |
GCF2 overexpression and siRNA knockdown, Western blot for RhoA and MRP1, immunofluorescence for actin/filamin/MRP1 localization, drug sensitivity assays |
Molecular pharmaceutics |
Medium |
22571463
|
| 2012 |
GCF2/LRRFIP1 promotes colorectal cancer metastasis by regulating RhoA interaction with the RGS domain of LARG (Leukemia Associated RhoGEF), thereby driving integrin-dependent RhoA activation, cell adhesion, migration, and invasion. |
Stable shRNA knockdown in HT-29 cells, in vivo spleen injection metastasis model (SCID mice), fibronectin-induced adhesion/migration/invasion assays, RhoA-LARG interaction analysis |
Cancer letters |
Medium |
22750095
|
| 2012 |
The FLI-interacting domain of LRRFIP1 forms a classic parallel homodimeric coiled coil with 10 heptad repeats and 22 helical turns, confirmed as a dimer in solution; a longer construct spanning the coiled-coil and DNA-binding domains assembles into higher-order oligomers in solution. |
X-ray crystallography of LRRFIP1 coiled-coil domain, solution biophysics (confirming dimer/oligomer state) |
Journal of structural biology |
High |
23099021
|
| 2013 |
LRRFIP1 induces vascular smooth muscle cell (VSMC) proliferation and increases phosphorylation of ERK; miR-132 blocks VSMC proliferation by directly targeting and downregulating LRRFIP1 via its 3′-UTR. |
miR-132 mimic/antagomir transfection, luciferase reporter assay with LRRFIP1 3′-UTR, Western blot for p27/SM α-actin/Bcl2, ERK phosphorylation assay, carotid artery injury model in rat |
Atherosclerosis |
Medium |
23880186
|
| 2014 |
LRRFIP1 binds directly to long noncoding RNAs upstream of the TNF gene and serves as part of a repressive complex assembled on these noncoding RNAs; knockdown of the noncoding RNAs reduced LRRFIP1 binding to both RNA targets and chromatin, leading to TNF derepression, while overexpression of the noncoding RNAs recruited repressor proteins including LRRFIP1 to the locus. |
RNA immunoprecipitation, ChIP, RNA knockdown and overexpression, five complementary identification methods for noncoding RNAs |
Journal of immunology |
Medium |
24567534
|
| 2014 |
In rat cortex after cerebral ischemia, Lrrfip1 (the main isoform) is upregulated from acute to late phases and localizes to the cytoplasm of neurons and astrocytes in the peri-infarct area. In astrocytes, Lrrfip1 activates β-catenin, Akt, and mTOR signaling and positively regulates expression of the glutamate transporter GLT-1. |
qPCR, immunohistochemistry, subcellular fractionation, in vivo and in vitro ischemia models, Western blot for pathway activation |
Neuroscience |
Medium |
24637094
|
| 2015 |
LRRFIP1 silencing in pancreatic and lung cancer cells reverses the epithelial-mesenchymal transition (EMT), evidenced by increased E-cadherin and decreased vimentin; mechanistically, LRRFIP1 silencing upregulates phosphorylation of β-catenin and decreases its nuclear localization by targeting the β-catenin destruction complex, while increasing β-catenin and E-cadherin in the plasma membrane fraction and inhibiting migration and invasion. |
siRNA knockdown, Western blot for EMT markers, subcellular fractionation for β-catenin localization, migration/invasion assays |
Cancer letters |
Medium |
26047573
|
| 2015 |
LRRFIP1 overexpression in hepatocytes increases IFN-β expression (with or without HCV infection) and inhibits HCV replication, establishing a role for LRRFIP1-mediated type I interferon induction in controlling HCV infection. |
LRRFIP1 overexpression in Huh7/Huh7.5.1 cells, qRT-PCR and Western blot for IFN-β, HCV replication assay |
Hepatitis monthly |
Low |
26045710
|
| 2017 |
Among LRRFIP1 isoforms, LRRFIP1-Iso1 is the strongest enhancer of the canonical Wnt/β-catenin transcription pathway; this activity requires a specific N-terminal domain harboring two critical tryptophan residues (W76, W82) and depends on LRRFIP1-Iso1 homodimerization governed by its specific coiled-coil domain. LRRFIP1-Iso1 and -Iso2 are primarily nuclear due to their shared C-terminal domain, whereas Iso3, -4, and -5 are primarily cytoplasmic and form homo/hetero-multimers. |
Topflash β-catenin reporter assay, site-directed mutagenesis (W76A, W82A), subcellular localization by immunofluorescence, co-immunoprecipitation for oligomerization, expression profiling |
Biochimica et biophysica acta. Molecular cell research |
High |
28322931
|
| 2019 |
LRRFIP1 expression triggers platelet agglutination by enhancing αIIbβ3 integrin expression; LRRFIP1 knockout in mice significantly decreased αIIbβ3 levels and inhibited platelet agglutination in response to collagen, thrombin, and convulxin. |
LRRFIP1 knockout mouse model, platelet aggregation apparatus, flow cytometry for active αIIbβ3 |
Experimental and therapeutic medicine |
Medium |
31258662
|
| 2020 |
LRRFIP1 is a novel interactor of DAPK1 (Death-Associated Protein Kinase 1) in neurons exposed to oxygen/glucose deprivation (OGD); LRRFIP1 protein levels are increased by pro-oxidant conditions (OGD or the ferroptosis inducer erastin), and the LRRFIP1–DAPK1 interaction was confirmed by reverse Co-IP. |
Co-immunoprecipitation (Co-IP and reverse Co-IP), LC-MS/MS proteomics, Western blot, OGD and erastin treatment of primary rat cortical neurons |
Antioxidants |
Low |
33265962
|
| 2021 |
LRRFIP1 silencing in pancreatic cancer cells sensitizes them to gemcitabine by activating the JNK/c-Jun signaling axis; gemcitabine-induced JNK and c-Jun phosphorylation are increased in LRRFIP1 knockdown cells, and this JNK/c-Jun activation depends on Rac activity, as Rac inhibition diminishes the effect. |
siRNA knockdown, caspase activity assay, phospho-Western blot for JNK/c-Jun, Rac inhibitor treatment, cell viability assays |
Pancreatology |
Medium |
33707114
|
| 2024 |
GCF2/LRRFIP1 mediates nicotine-induced HCC cancer stemness and progression by activating the Wnt/β-catenin/SOX2 signaling pathway; nicotine stabilizes GCF2 protein levels, and silencing GCF2 reduces nicotine-induced stemness and progression. |
GCF2 siRNA knockdown, overexpression, Western blot for Wnt/β-catenin/SOX2 pathway components, cancer stemness assays |
Ecotoxicology and environmental safety |
Low |
38218109
|
| 2025 |
LRRFIP1 enhances canonical Wnt/β-catenin signaling in MDS cells by binding to DVL2 and DVL3 (Dishevelled proteins); LRRFIP1 and Dvl synergistically increase Wnt pathway activity, upregulate β-catenin, Dvl2, Dvl3, BCL-2, and CyclinD1, and promote MDS cell proliferation while inhibiting apoptosis. |
mRNA transcriptome sequencing, dual luciferase reporter assay, Western blot, co-overexpression experiments (LRRFIP1/Dvl3), CCK8, Annexin-V apoptosis assays |
Journal of translational medicine |
Medium |
40420163
|
| 2025 |
LRRFIP1 inhibits white adipocyte differentiation by binding to the E2F6 promoter and suppressing E2F6 transcription, which in turn downregulates C/EBPα; silencing LRRFIP1 inhibits adipogenic differentiation in C3H10T1/2 cells and reduces differentiation biomarker expression, while overexpression has the opposite effect. |
Chromatin immunoprecipitation (ChIP), luciferase promoter assay, qRT-PCR, Western blot, C3H10T1/2 adipogenic differentiation assay, diet-induced obesity mouse model |
Diabetes & metabolism journal |
Medium |
41224206
|
| 2026 |
In tumor-associated macrophages (TAMs), LRRFIP1 promotes M2-like macrophage polarization via the PI3K/AKT signaling pathway; LRRFIP1 knockdown suppresses M2 phenotype and related cytokine expression, and inhibition of the PI3K pathway or TGF-β receptor abolishes further effects of LRRFIP1 knockdown. |
siRNA knockdown in TAMs, flow cytometry, Western blot for PI3K/AKT, ELISA for cytokines, Transwell invasion assay, in vivo tumor/metastasis models, PI3K inhibitor epistasis experiment |
Journal of translational medicine |
Medium |
41612403
|