| 1994 |
90K/LGALS3BP is a secreted glycoprotein carrying a scavenger receptor cysteine-rich (SRCR) domain, and stimulates natural killer cell and lymphokine-activated killer cell activity, with immunostimulatory effects potentially mediated through induction of interleukin-2. |
Monoclonal antibody-based protein purification, Northern blot, functional NK/LAK cell assays, cytokine induction assays |
The Journal of biological chemistry |
Medium |
8034587
|
| 1995 |
Engineered enhancement of 90K expression in tumor cell lines results in significant (>80%) tumor growth inhibition in athymic mice, not by direct action on tumor cells, but by stimulation of residual cell-mediated immune defense, and involves induction of ICAM-1 and VCAM-1 in tumor endothelium. |
Stable overexpression in mammary carcinoma and glioblastoma cell lines, xenograft tumor growth assays in nude mice, immunohistochemistry for ICAM-1/VCAM-1 |
Cancer research |
Medium |
7542166
|
| 1988 |
Recombinant interferon-alpha 2b stimulates de novo synthesis and secretion of 90K in human breast cancer cells in a dose-dependent manner, an effect blocked by cycloheximide, indicating transcriptional/translational regulation by IFN-alpha. |
Cell culture treatment with rIFN-alpha 2b, immunoassay of conditioned media, cycloheximide block experiment, in vivo patient serum measurement |
International journal of cancer |
Medium |
3403063
|
| 2001 |
90K/LGALS3BP interacts with galectin-1 at a site distinct from the galectin-3 binding site (the two galectins do not compete), with a dissociation constant of ~10^-7 M, and galectin-1-induced aggregation of melanoma A375 cells is mediated at least in part by 90K, as shown by inhibition with anti-90K monoclonal antibody. |
Solid-phase binding assay with recombinant proteins, lactose-inhibition controls, competitive binding assay, cell aggregation assay with blocking antibody |
International journal of cancer |
Medium |
11146440
|
| 2008 |
Endosialin (Tem1), expressed by tumor stromal fibroblasts, directly binds Mac-2 BP/90K; the C-terminal fragment of Mac-2 BP/90K (containing binding sites for galectin-3 and collagens) is responsible for endosialin binding. This interaction is repulsive: adhesion of Mac-2 BP/90K-expressing tumor cells on endosialin-expressing fibroblasts yields a repulsive outcome. |
Affinity chromatography, biochemical binding assays with domain deletion constructs, loss-of-function adhesion experiments, in vivo expression analysis |
FASEB journal |
Medium |
18490383
|
| 2010 |
90K interacts with the CD9/CD82 tetraspanin complex and suppresses Wnt/beta-catenin signaling via a novel ISG15 (ISGylation)-dependent ubiquitination/proteasomal degradation of beta-catenin that is independent of GSK-3beta and Siah/APC. In a syngeneic mouse colon tumor model, 90K knockdown increased tumor growth and lung metastasis. |
Co-immunoprecipitation, cell invasion assays, ISGylation pathway manipulation, syngeneic mouse tumor model, immunohistochemistry of human CRC tissues |
Gut |
High |
20581239
|
| 2013 |
LGALS3BP is a centriole- and basal body-associated protein with a dual role: overexpression triggers centrosome hypertrophy, while knockdown causes accumulation of centriolar substructures (comprising CPAP, acetylated tubulin and centrin). Depletion of LGALS3BP in cells endogenously overexpressing it reverses centrosome hypertrophy. |
Protein-interaction network screen, siRNA knockdown, overexpression, immunofluorescence microscopy, analysis of cancer cell lines and seminoma tissue |
Nature communications |
High |
23443559
|
| 2013 |
LGALS3BP constitutes a novel integrin ligand for integrins alpha1beta1, alpha5beta1, alphavbeta1, and alpha6beta1, and LGALS3BP-mediated integrin activation transmits signals via Akt, JNK, Ras/Raf-ERK, while keeping p38 at baseline. Sustained LGALS3BP exposure supports cell viability, motility and migration, and anti-LGALS3BP antibody SP2 impedes these signaling events. |
Integrin-binding assays, phosphorylation/signaling assays (Akt, JNK, ERK, p38), cell adhesion, viability, migration assays, antibody blocking experiments |
Oncogene |
Medium |
24362527
|
| 2013 |
90K/LGALS3BP is an interferon-stimulated gene product that dose-dependently decreases HIV-1 particle infectivity by impairing gp160 processing and reducing incorporation of mature gp120/gp41 into virions, without directly interacting with HIV-1 Env or entrapping Env in the ER. The two intermediate domains of 90K are sufficient for antiviral activity; the N-terminal SRCR and C-terminal domains are dispensable. siRNA knockdown of 90K in macrophages enhanced Env incorporation and HIV-1 spread. |
Overexpression/siRNA knockdown in producer cells, HIV-1 infectivity assays, Western blot for viral proteins, domain truncation mutants, IFN-alpha treatment of macrophages |
Retrovirology |
High |
24156545
|
| 2014 |
LGALS3BP is identified as a sialic acid-dependent ligand for the immunomodulatory Siglec-9 (and Siglec-5 and Siglec-10) via affinity chromatography of tumor cell extracts; LGALS3BP inhibits neutrophil activation in a sialic acid- and Siglec-dependent manner. The mouse homolog binds murine Siglec-E with lower affinity. |
Affinity chromatography of tumor cell extracts, Siglec binding assays, sialic acid-dependency experiments, neutrophil activation assays |
The Journal of biological chemistry |
Medium |
25320078
|
| 2012 |
LGALS3BP knockdown in MDA-MB-231 breast cancer cells decreases adhesion to fibronectin, reduces transendothelial migration, and reduces VEGF expression; VEGF production was restored by exogenous recombinant LGALS3BP and requires intact PI3K/Akt signaling. Additionally, LGALS3BP directly stimulates HUVEC tubulogenesis in a VEGF-independent, galectin-3-dependent manner. |
siRNA knockdown, VEGF ELISA, PI3K inhibitor rescue, HUVEC tubulogenesis assay, anti-galectin-3 blocking, adhesion and migration assays |
Journal of molecular medicine |
Medium |
22864925
|
| 2019 |
LGALS3BP functions as a scaffold/adaptor protein that interacts with TRAF6, TRAF3, TAK1, and TBK1; it enhances TRAF6 and TRAF3 ubiquitination, is itself a ubiquitination substrate of TRAF6, and promotes NF-κB, IRF3, and IRF7 nuclear translocation, leading to IFN and pro-inflammatory cytokine production upon viral infection. |
Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, overexpression, reporter assays for NF-κB/IRF3/IRF7 activity, viral infection models |
PLoS pathogens |
High |
31404116
|
| 2016 |
M2BP/90K inhibits HIV-1 virion production by trapping HIV-1 Gag to vimentin filaments to inhibit Gag trafficking to the plasma membrane. M2BP interacts with both HIV-1 Gag and vimentin. Collapsing vimentin filaments (by acrylamide or dominant-negative vimentin) relieves M2BP-mediated inhibition of virion production. |
Co-immunoprecipitation (M2BP with Gag and vimentin), vimentin disruption experiments, HIV-1 virion production assays, dominant-negative vimentin overexpression |
Scientific reports |
Medium |
27604950
|
| 2018 |
The antiviral activity of 90K/LGALS3BP against HIV-1 is conserved across most primate orthologs but absent in rhesus macaque 90K. A single amino acid exchange in the BTB/POZ domain restores antiviral activity in a shortened rhesus macaque 90K. Structural analysis of BTB/POZ domains from rhesus macaque and human 90K reveals a slightly larger hydrophobic patch in rhesus macaque that may modulate protein-protein interactions. Reduction of virion-associated gp120, not merely reduced cell-surface gp120, correlates with antiviral activity. |
Comparative ortholog expression assays, HIV-1 infectivity assays, domain mutagenesis, X-ray crystallography of BTB/POZ domains |
Journal of virology |
High |
29743357
|
| 2006 |
TAA90K/Mac-2-binding protein purified from colon cancer cells binds fibronectin, collagen IV, laminins-1/-5/-10, and galectin-3 in solid-phase assays; binding to galectin-3 is carbohydrate-dependent (inhibited by lactose and asialo-fetuin) and requires proper N-glycosylation. At low concentrations, TAA90K enhances galectin-3-mediated HT-29 cell adhesion; at high concentrations it inhibits adhesion. |
Protein purification from vaccinia-virus-expressed TAA90K, solid-phase binding assays, glycosylation inhibitor (1-deoxymannojirimycin), lactose inhibition, cell adhesion assays |
Journal of cellular biochemistry |
Medium |
16518858
|
| 2009 |
TAA90K/Mac-2-binding protein is a novel substrate for matrix metalloproteinases MMP-2, MMP-7, and MMP-9; MMP-7-mediated cleavage of TAA90K reduces its interaction with fibronectin and laminin-10 but not with laminin-1, collagen IV, or galectin-3. TAA90K also enhances extracellular levels of proMMP-7 in HT-29 colon cancer cells. |
SDS-PAGE and protein sequencing of cleavage products, solid-phase binding assays before and after cleavage, ELISA for proMMP-7 levels |
Biochimica et biophysica acta |
Medium |
19665518
|
| 2017 |
90K promotes E-cadherin degradation via ubiquitination-mediated proteasomal degradation. 90K interacts with the E-cadherin-p120-catenin complex, induces its dissociation, and alters the phosphorylation status of p120-catenin, but does not associate with beta-catenin. This effect is cell-density-dependent and is diminished in p120-catenin knockdown cells. |
Co-immunoprecipitation, ubiquitination assays, proteasome inhibitor treatment, p120-catenin siRNA knockdown, cell adhesion and invasion assays |
International journal of molecular sciences |
Medium |
29207493
|
| 2016 |
90K-mediated beta-catenin degradation via ISGylation requires the N-terminal 86 amino acids of beta-catenin. 90K induces Herc5 and ISG15 expression; the N-terminus of beta-catenin is not essential for interaction with Herc5, but is required for 90K-induced degradation. 90K can degrade mutant beta-catenin lacking GSK-3beta phosphorylation sites, indicating a phosphorylation-independent degradation pathway. |
Beta-catenin deletion and point mutants, Western blot, co-immunoprecipitation, overexpression in HeLa and CSC221 cells |
Neoplasia |
Medium |
27668402
|
| 2021 |
LGALS3BP suppresses colon inflammation and tumorigenesis by downregulating the TAK1-NF-κB signaling axis in colon epithelial cells. Lgals3bp-/- mice show hyperactivated NF-κB, excessive pro-inflammatory cytokines (IL-6, TNFα, IL-1β), elevated GM-CSF, and accumulation of myeloid-derived suppressor cells during tumorigenesis. |
Lgals3bp-/- knockout mice, colitis and colon tumor models, NF-κB reporter/activation assays, cytokine measurement, MDSC quantification |
Cell death discovery |
High |
33824294
|
| 2023 |
LGALS3BP suppresses TNF-alpha-mediated MMP9 gene expression in triple-negative breast cancer by inhibiting activation of TAK1 kinase, the key signaling node linking TNF-α and MMP9 expression. Nanoparticle-delivered LGALS3BP inhibits TAK1 phosphorylation and MMP9 expression in tumors and suppresses lung metastasis in vivo. |
LGALS3BP overexpression/knockdown, TNF-alpha stimulation, TAK1 phosphorylation assays, MMP9 reporter/ELISA, nanoparticle delivery in vivo, xenograft metastasis model |
Cell death discovery |
Medium |
37041137
|
| 2024 |
LGALS3BP directly binds integrin αV and promotes assembly of integrin αV complexes, enabling release of active TGF-β1 from the extracellular latent complex with rearrangement of F-actin cytoskeleton. Released TGF-β1 activates JunB transcription factor, creating a positive feedback loop for TGF-β1 production. Hepatocyte-specific LGALS3BP knockin mice show aggravated liver fibrosis with increased TGF-β1; LGALS3BP knockout reduces TGF-β1 signaling and CCl4-induced fibrosis. |
Co-immunoprecipitation (LGALS3BP with integrin αV), LC-MS/MS proteomics, RNA-seq, ATAC-seq, conditional knockin/knockout mice, CCl4 fibrosis model, F-actin cytoskeleton analysis |
Cancer communications |
High |
39073023
|
| 2021 |
LGALS3BP is a secreted protein enriched in human neural progenitor cells (NPCs) that regulates the position of NPCs; LGALS3BP-mediated mechanisms involve the extracellular matrix in NPC anchoring and migration. Its temporal expression influences NPC delamination, corticogenesis, and gyrification, demonstrated in cerebral organoids, human fetal tissue, and mouse models. |
Cerebral organoids, human fetal tissue analysis, mouse in utero experiments, single-cell RNA-sequencing, proteomics, analysis of individuals with de novo LGALS3BP variants |
Nature communications |
High |
34728600
|
| 2017 |
WFA+-M2BP (glycosylated LGALS3BP) is secreted by hepatic stellate cells (HSCs). Exogenous WFA+-M2BP stimulation enhances Mac-2/galectin-3 expression in Kupffer cells; Mac-2-depleted Kupffer cells (siRNA) show reduced alpha-smooth muscle actin expression when co-cultured with HSCs, establishing a paracrine circuit: HSC-secreted LGALS3BP→Kupffer cell Mac-2 expression→Kupffer cell activation→HSC fibrogenic activation. |
Subpopulation cell culture with sandwich immunoassay, siRNA knockdown of Mac-2 in Kupffer cells, co-culture experiments, immunoblot, liver tissue immunohistochemistry |
Journal of gastroenterology and hepatology |
Medium |
28008658
|
| 1997 |
The 90K protein domain structure was mapped: an N-terminal SRCR-like domain (D1), a heavily glycosylated mucin-like domain (D2), and a ~27 kDa C-terminal domain (D3). Monoclonal antibodies SP2 and L3 both recognize D2. Point mutations at residues 189, 223, and 259 and a truncated form (aa 1-383) are defective in secretion, identifying specific residues required for normal processing and secretion. |
Ig fusion protein construction with domain deletions, monoclonal antibody epitope mapping, COS-1 cell expression, secretion assays with point mutants |
Biochemical and biophysical research communications |
Medium |
9125183
|
| 1999 |
The human 90K promoter is TATA-less, lacks GC-richness and SP1 dependence, has a minimal promoter of 51 bp, and contains an interferon regulatory factor element (IRF-E) required for induction by poly(I:C) (viral mimic) and interferon-gamma. Two regions mediating poly(I:C) induction were identified by deletion analysis. |
Promoter deletion analysis, RNase protection assay for transcription start sites, point mutations in the IRF-E, poly(I:C) stimulation, reporter gene assays |
Genomics |
Medium |
10198166
|
| 2007 |
Constitutive expression of 90K/LGALS3BP depends on upstream stimulatory factor (USF) binding to an E-box in the minimal promoter. Hormonal suppression (TSH/cAMP plus insulin/IGF-I) of constitutive and IFN-gamma-induced 90K expression occurs via decreased USF binding to this E-box. Transfection with USF1/USF2 cDNAs increases constitutive promoter activity and attenuates hormonal suppression. |
Promoter cloning, EMSA (electrophoretic mobility shift assay) for USF binding, transfection with USF1/USF2 expression plasmids, reporter gene assays, TSH/cAMP/insulin treatments |
Endocrinology |
Medium |
17446190
|
| 1996 |
Exposure of the human breast cancer cell line EVSA-T to purified 90K protein causes approximately sixfold increase in MHC class I expression as measured by flow cytometry, demonstrating a direct effect of secreted 90K on immune recognition molecules. |
Purified 90K protein treatment of cancer cells, flow cytometry for MHC class I expression |
Biochemical and biophysical research communications |
Low |
8753808
|
| 2019 |
GALNT6 O-glycosylates LGALS3BP at three sites (T556, T571, S582), and this O-glycosylation is required for LGALS3BP secretion and autocrine growth promotion in breast cancer cells. Triple Ala substitution (T556A/T571A/S582A) drastically reduces GALNT6-dependent LGALS3BP O-glycosylation and secretion, suppressing autocrine growth. |
GALNT6 siRNA knockdown, O-glycosylation site mutagenesis (T→A substitutions), LGALS3BP secretion assay, cell growth assay |
International journal of oncology |
Medium |
31894262
|
| 2016 |
Mac-2 binding protein (M2BP) is identified as a novel serum adiponectin-binding protein by immunoprecipitation with anti-adiponectin antibody followed by mass spectrometry; the M2BP-APN association was confirmed with reconstituted proteins in vitro. M2BP abrogates the suppressive effect of adiponectin on TNF-alpha-induced inflammation in vascular endothelial cells. |
Immunoprecipitation with anti-adiponectin antibody, mass spectrometry, in vitro reconstitution with purified proteins, endothelial cell inflammation assay |
Atherosclerosis |
Medium |
27588936
|
| 2023 |
In platelets from SLE patients, interferon-alpha induces LGALS3BP transcription and translation in megakaryoblastic cells in a dose-dependent manner. Platelet-released LGALS3BP and recombinant LGALS3BP enhance proinflammatory cytokine production by macrophages, establishing a platelet-to-macrophage proinflammatory signaling role for LGALS3BP. |
RNA sequencing of SLE patient platelets, IFN-alpha treatment of MEG-01 cells, ELISA for platelet releasate LGALS3BP, macrophage cytokine production assays with recombinant LGALS3BP |
Arthritis & rheumatology |
Medium |
36245285
|
| 2024 |
LGALS3BP is broadly expressed in the CNS and upregulated during WNV infection and aging; Lgals3bp-deficient mice exhibit reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell populations after WNV encephalitis recovery, without differences in virologic control or survival, indicating a role in regulating microglial activation and neuroinflammation. |
Spatial transcriptomics, RNA sequencing, flow cytometry, Lgals3bp-knockout mouse model, WNV infection model |
Biomolecules |
Medium |
39062523
|
| 2025 |
LGALS3BP expression in tamoxifen-resistant breast cancer is suppressed by estrogen signaling through direct ERα binding to the LGALS3BP promoter. Secreted LGALS3BP promotes adhesion to the extracellular matrix and HUVEC tube formation. LGALS3BP knockdown in tamoxifen-resistant cells completely abrogated increased pulmonary metastasis in xenograft experiments. |
Chromatin immunoprecipitation (ERα to LGALS3BP promoter), TurboID secretome labeling, shRNA knockdown, HUVEC tube formation assay, xenograft metastasis model |
Breast cancer research |
Medium |
39789641
|