| 2015 |
WDFY1 acts as a crucial adaptor protein in TLR3/4 signaling by physically interacting with TLR3 and TLR4 and mediating the recruitment of TRIF to these receptors, thereby enabling downstream NF-κB and IRF3 activation and type I interferon production. Overexpression potentiates signaling; depletion has the opposite effect. |
Co-immunoprecipitation, overexpression/knockdown experiments with NF-κB/IRF3 reporter assays, cytokine measurements |
EMBO reports |
High |
25736436
|
| 2022 |
WDFY1 is a component of a CUL4A-DDB1-WDFY1 E3 ubiquitin ligase complex that is essential for initiating lysophagy; the complex ubiquitinates LAMP2 on damaged lysosomes to trigger their autophagic clearance. |
Proteomic studies using transfection reagent-coated beads, further functional evaluations, E3 ligase activity assays, identification of LAMP2 as substrate |
Cell reports |
High |
36103833
|
| 2016 |
NRP2 negatively regulates WDFY1 expression at the transcriptional level by preventing nuclear localization of the transcription factor FAC1, thereby maintaining WDFY1 at levels compatible with sustained endocytic activity in metastatic cancer cells. |
Transcriptional reporter assays, nuclear localization analysis of FAC1, NRP2 knockdown/overexpression with WDFY1 expression readouts |
Scientific reports |
Medium |
27026195
|
| 2019 |
The transcription factor Hes1 suppresses type I IFN production by inhibiting WDFY1 expression indirectly: Hes1 directly binds and upregulates VEGF-C expression, which in turn downregulates WDFY1, attenuating TLR upstream signaling. |
Genome-wide ChIP-seq for Hes1 occupancy, Hes1 knockout mice, WDFY1 expression analysis, IFN production assays |
The Journal of experimental medicine |
Medium |
31015298
|
| 2022 |
WDFY1 protein is expressed in mouse testes, localizing to the cytoplasm of late pachytene spermatocytes to elongated spermatids; however, global Wdfy1 knockout male mice show normal spermatogenesis and fertility, demonstrating WDFY1 is dispensable for these processes. |
Transgenic FLAG-Wdfy1-mCherry reporter mice for localization; global Wdfy1 knockout mice with histological analysis of testes and fertility testing |
Biochemical and biophysical research communications |
Medium |
35121371
|
| 2026 |
Aged brain neurons secrete WDFY1 protein via extracellular vesicles (EVs) that are transferred to bone, where WDFY1 binds to the retromer complex to promote endosome-to-Golgi recycling of cathepsin D and peroxiredoxin 2, thereby inhibiting osteogenesis and augmenting adipogenesis, causing bone-fat imbalance and osteoporosis. |
Neuronal Wdfy1 knockout mice, EV inhibition experiments, co-immunoprecipitation (WDFY1-retromer interaction), gain/loss-of-function in brain-specific models, bone phenotype analysis |
Nature aging |
Medium |
41491871
|
| 2025 |
WDFY1 expression in follicular dendritic cells (FDCs) is required for immune complex (IC) presentation; WDFY1 knockout impairs IC binding to FDCs, reduces germinal center formation, and diminishes autoantibody production in a cGVHD lupus mouse model. B cells and T cells lacking WDFY1 retain normal intrinsic function, indicating the defect is FDC-intrinsic. |
WDFY1 knockout mice in cGVHD model, immunofluorescence for IC-FDC binding, mixed leukocyte reaction, B-cell reconstitution in Rag1-KO mice, autoantibody titers |
Journal of immunology |
Medium |
40169152
|
| 2025 |
In murine mesangial cells, a 500 bp distal fragment upstream of the wdfy1 5'-UTR drives approximately four-fold enhanced promoter activity; transcription factors Sp1, Ap-1, Hes1, and TCF7 bind sites in the promoter/5'-UTR to regulate WDFY1 expression; the 3'-UTR suppresses expression (~3.5-fold); IL-6 upregulates WDFY1 through Sp1. |
Luciferase reporter assays with promoter deletion mutants, siRNA knockdown of transcription factors, IL-6 stimulation of primary renal mesangial cells |
Cells |
Medium |
40497974
|
| 2025 |
Grass carp WDFY1 (CiWDFY1) physically interacts with TLR3, and TLR3 recruits both TRIF and CiWDFY1 to form an activated complex leading to IRF3 phosphorylation and nuclear translocation and IFN1 induction; CiWDFY1 knockdown disrupts the TLR3-TRIF physical interaction. Upon poly(I:C) stimulation, CiWDFY1 redistributes from diffuse cytoplasmic to perimembranous localization. |
Co-immunoprecipitation, co-localization assays, overexpression and knockdown in CIK cells, subcellular localization imaging, IRF3 phosphorylation/translocation assays |
Fish physiology and biochemistry |
Medium |
40748571
|
| 2018 |
WDFY1 siRNA knockdown decreases differentiation ability of primary neural stem cells; introduction of WDFY1 plasmid rescues reduced TLR4 expression and neurogenesis in neural stem cells from PRDX6-overexpressing transgenic mice, placing WDFY1 downstream of PRDX6 and upstream of TLR4 in a neurogenesis pathway. |
siRNA knockdown, plasmid rescue experiment in primary neural stem cells, neurogenesis assays, microarray identification of WDFY1 downregulation in PRDX6-Tg mice |
Molecular neurobiology |
Low |
30097850
|