Array MAPPIT: high-throughput interactome analysis in mammalian cells.
A proteome-scale map of the human interactome network.
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
A High-Density Map for Navigating the Human Polycomb Complexome.
A reference map of the human binary protein interactome.
The FBXL family of F-box proteins: variations on a theme.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Multimodal cell maps as a foundation for structural and functional genomics.
Falcon deep research report for human FBXL8
-
FBXL8 is the substrate-recognition adaptor of an SCF E3 ubiquitin ligase whose net biological effect is strongly context-dependent rather than uniformly oncogenic or tumor-suppressive.
"FBXL8 is an SCF-type E3 ubiquitin ligase substrate receptor (F-box + LRR protein) that determines substrate specificity and promotes ubiquitination of distinct targets in a context-dependent manner, influencing proteasomal degradation or other ubiquitin-mediated outcomes"
-
SCF-FBXL8 binds p53, increases its ubiquitination and accelerates its turnover in colorectal cancer; both the F-box and the C-terminal region are required.
"FBXL8 physically associates with p53 (co-immunoprecipitation), increases p53 ubiquitination, and accelerates p53 turnover in cycloheximide chase experiments; **both the F-box and LRR regions are required** for this effect, because ΔFbox and ΔLRR constructs fail to influence p53 stability like full-length FBXL8"
-
SCF-FBXL8 recognizes Thr283-phosphorylated cyclin D3 and drives its proteasomal degradation, suppressing lymphoma growth.
"FBXL8 (as SCF-FBXL8) recognizes **Thr-283 phosphorylated cyclin D3**, polyubiquitylates it, and drives proteasomal degradation."
-
In post-myocardial-infarction cardiac fibroblasts FBXL8 promotes ubiquitin-proteasome degradation of Snail1, reducing RhoA activation and myofibroblast differentiation.
"In post-myocardial infarction (MI) remodeling, FBXL8 interacts with **Snail1** and promotes its **ubiquitin–proteasome degradation**, with a defined interaction requirement (FBXL8 ΔC3 domain requirement). This down-modulates downstream **RhoA activation** and dampens myofibroblast differentiation"
-
FBXL8 recognizes and ubiquitylates unphosphorylated c-MYC, a distinct pool from that controlled by FBXW7, and is reported to be largely cytoplasmic.
"FBXL8 recognizes and ubiquitylates **unphosphorylated c-MYC**, distinct from the canonical phospho-degron recognition by FBXW7. Concurrent loss of FBXL8 and FBXW7 additively elevates c-MYC, consistent with regulation of distinct c-MYC pools."
AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex
NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex
CAND1 binds cytosolic CRL E3 ubiquitin ligases
COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex
Transfer of Ub from E2 to substrate and release of E2
Release of E3 from polyubiquitinated substrate
Polyubiquitination of substrate
Interaction of E3 with substrate and E2-Ub complex