| 2020 |
SCF-Fbxl8 is identified as the E3 ubiquitin ligase for phospho-Thr-283 cyclin D3; it poly-ubiquitylates p-Thr-283 cyclin D3 targeting it for proteasomal degradation, thereby antagonizing cell cycle progression, hematopoietic cell proliferation, and oncogene-induced transformation. |
Co-immunoprecipitation, ubiquitylation assays, cyclin D3T283A phosphorylation-deficient mutant rescue experiments, cell proliferation and transformation assays |
Oncogene |
High |
33122824
|
| 2022 |
SCF-Fbxl8 binds and ubiquitylates c-myc independent of phosphorylation (i.e., independent of the Fbxw7 phospho-degron), targeting a distinct pool of c-myc for degradation; loss of Fbxl8 increases c-myc protein levels and stability and increases cell division, while concurrent loss of Fbxl8 and Fbxw7 causes a synergistic increase in c-myc protein. |
Co-immunoprecipitation, ubiquitylation assay, loss-of-function (Fbxl8 knockdown/loss), gain-of-function (Fbxl8 overexpression), protein stability assay, double-loss epistasis (Fbxl8 + Fbxw7) |
Cancer biology & therapy |
High |
35438057
|
| 2020 |
FBXL8, as an E3 ubiquitin ligase, interacts with (by Co-IP) and promotes degradation of CCND2 (cyclin D2) and IRF5 in breast cancer cells; knockdown of FBXL8 causes accumulation of CCND2 and IRF5, induces apoptosis, and inhibits cell migration and invasion. |
Co-immunoprecipitation, FBXL8 knockdown with protein accumulation readout, cell migration/invasion assays, apoptosis assays |
Cancers |
Medium |
32784654
|
| 2021 |
FBXL8 and FZR1 each independently pull down CCNF (cyclin F); double knockdown of both FBXL8 and FZR1 causes CCNF protein accumulation, indicating both E3 ligases contribute to CCNF degradation in breast cancer cells. |
Co-immunoprecipitation (pulldown), double knockdown with protein accumulation readout |
Cancers |
Medium |
34201347
|
| 2023 |
SCF-FBXL8 directly interacts with and ubiquitinates TP53 (p53), promoting its degradation via the proteasome in colorectal cancer cells; FBXL8 knockout stabilizes p53 and inhibits tumor proliferation, invasion, migration, stem-cell-like properties, and liver metastasis in vivo. |
Co-immunoprecipitation, ubiquitination assay, FBXL8 knockout, xenograft mouse model, western blotting |
Clinical and translational medicine |
Medium |
36855778
|
| 2024 |
FBXL8 interacts with Snail1 via its C3-binding domain and promotes Snail1 degradation through the ubiquitin-proteasome system, leading to decreased RhoA activation; FBXL8 overexpression in cardiac fibroblasts suppresses TGFβ-induced fibroblast activation (proliferation, migration, contraction, collagen secretion), and AAV9-mediated FBXL8 overexpression ameliorated post-myocardial infarction cardiac fibrosis in vivo. |
Co-immunoprecipitation, proteasome inhibition assay, FBXL8ΔC3 deletion mutant, FBXL8 overexpression/knockdown in cardiac fibroblasts, Snail1 rescue experiments, AAV9-mediated overexpression in MI mouse model, echocardiography and histology |
Cell death & disease |
High |
38615011
|
| 2026 |
FBXL8 binds dephosphorylated IκBα (at S32/S36) and mediates K63-linked polyubiquitination at the K38 site of IκBα, thereby stabilizing IκBα (non-degradative ubiquitination) and inhibiting NF-κB p65 nuclear translocation; additionally, NF-κB p65 transcriptionally upregulates YY1, which in turn transcriptionally represses FBXL8, forming a feedforward loop. |
Co-immunoprecipitation, ubiquitination assay (K63-linkage-specific), site-directed mutagenesis (K38), dephosphorylation experiments, NF-κB p65 nuclear translocation assay, transcription factor binding (YY1-ChIP implied), in vitro and in vivo functional assays |
International journal of biological sciences |
High |
41608629
|