| 2018 |
C1orf106/INAVA regulates adherens junction stability by controlling the degradation of cytohesin-1, a guanine nucleotide exchange factor. By limiting cytohesin-1-dependent ARF6 activation, C1orf106 stabilizes adherens junctions. The IBD risk variant increases C1orf106 ubiquitination and turnover, leading to impaired barrier function. C1orf106-/- mice exhibit defects in intestinal epithelial cell barrier. |
Knockout mouse model, degradation assays for cytohesin-1, ARF6 activation assays, ubiquitination assays |
Science (New York, N.Y.) |
High |
29420262
|
| 2017 |
INAVA is required for optimal MAPK and NF-κB activation, cytokine secretion, and intracellular bacterial clearance upon PRR stimulation in primary human myeloid cells. INAVA recruits 14-3-3τ to form a signaling complex that amplifies downstream signals. INAVA also enhances bacterial clearance by regulating reactive oxygen species, reactive nitrogen species, and autophagy pathways. |
siRNA knockdown in primary human macrophages, Co-immunoprecipitation for 14-3-3τ recruitment, cytokine ELISA, MAPK/NF-κB pathway activation assays, bacterial clearance assays |
The Journal of clinical investigation |
High |
28436939
|
| 2018 |
INAVA's DUF3338 domain (renamed CUPID) stably binds the cytohesin ARF-GEF ARNO to effect lateral membrane F-actin assembly underlying cell-cell junctions and barrier function. When bound to CUPID, ARNO affects F-actin dynamics independently of its canonical GEF activity. Upon IL-1β exposure, INAVA relocates to cytosolic puncta where CUPID amplifies TRAF6-dependent polyubiquitination and inflammatory signaling. ARNO binding to CUPID negatively regulates polyubiquitination and the inflammatory response. |
Domain mapping, Co-IP/pulldown of CUPID-ARNO interaction, F-actin assembly assays, GEF activity assays, polyubiquitination assays, live-cell imaging of INAVA relocalization, macrophage primary cell experiments |
eLife |
High |
30355448
|
| 2018 |
C1ORF106 directly interacts with cytohesins to maintain functional epithelial cell junctions. C1orf106-deficient mice are hypersensitive to TNF-α-induced increase in epithelial permeability. |
Direct interaction assay (C1ORF106 with cytohesins), C1orf106 KO mouse model, TNF-α-induced permeability assay |
ImmunoHorizons |
Medium |
31022698
|
| 2021 |
IL-1β-induced INAVA cytosolic puncta are biomolecular condensates that rapidly assemble and physiologically resolve. The condensates contain ubiquitin and the E3 ligase βTrCP2, and their formation correlates with amplified ubiquitination, suggesting a role in cellular proteostasis regulation. Inhibitors of p38α and mTOR pathways enhanced resolution of condensates, while inhibitors of the Rho-ROCK pathway recruited INAVA to newly assembled intercellular junctions. |
Live-cell imaging of condensate dynamics, small-molecule screen, co-localization of βTrCP2 and ubiquitin with INAVA puncta, pharmacological pathway inhibition |
The Journal of cell biology |
Medium |
34251416
|
| 2025 |
C1ORF106 knockdown leads to impaired cortical actin belt dynamics, stress fiber dysregulation, increased cell constriction, impaired barrier permeability, cell polarity defects, and impaired cell migration. ROCK inhibition rescues the actin belt and cell polarity phenotypes in C1ORF106 KD cells, demonstrating that C1ORF106 regulates these phenotypes through a ROCK-dependent mechanism. Altered non-muscle myosin II phosphorylation (nmMYO2-P) localization was observed in C1ORF106 KD cells, associated with Vacuolar Apical Compartment (VAC) formation. The IBD-associated 333F variant in hiPSC-derived intestinal spheroids showed similar cell polarity impairments. |
siRNA knockdown in human colonic epithelial cells, hiPSC-derived intestinal spheroid cultures, immunofluorescence, western blots, permeability assays, ROCK inhibitor rescue experiments |
bioRxiv : the preprint server for biologypreprint |
Medium |
40161582
|
| 2018 |
INAVA upregulation in papillary thyroid cancer cells promotes invasion, migration, and metastasis through elevated FGF1 expression, which in turn increases MMP9 expression. |
Gain- and loss-of-function assays, transcriptome resequencing, western blotting, in vitro and in vivo metastasis assays |
Cell & bioscience |
Low |
29632659
|
| 2025 |
INAVA protein (translated from EV-delivered mRNA) competitively binds HMGA2 and inhibits its interaction with vaccinia-related kinase 1 (VRK1), leading to reduced HMGA2 phosphorylation at Ser105. This reduced phosphorylation stabilizes HMGA2 by blocking TRIM21-mediated K48-linked ubiquitylation, ultimately enhancing STAT3 transcription to activate normal ovarian fibroblasts. A cell-permeable peptide disrupting the INAVA-HMGA2 interaction attenuated fibroblast activation. |
Co-immunoprecipitation (INAVA-HMGA2 and HMGA2-VRK1), phosphorylation site mapping, ubiquitination assays (K48-linked), STAT3 transcription assays, peptide competition assay, orthotopic xenograft mouse model |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
40265981
|