FBXL17 (UniProt: Q8NEE6), also known as FBX13 or FBXO13, is a 83924 Da protein encoded by the FBXL17 gene (Gene ID: 222235) . Key features include:
Domain Structure: Contains an F-box motif (~40 amino acids) for binding SKP1 in SCF (SKP1-CUL1-F-box) ubiquitin ligase complexes .
Function: Regulates protein degradation via ubiquitination, influencing iron homeostasis, autophagy, and hypoxia responses .
Disease Relevance: Linked to colorectal cancer progression, metastasis, and chemoresistance .
Colorectal Cancer: FBXL17 knockout (KO) in DLD-1 and SW480 cells reduces wound healing, colony formation, and chemoresistance to platinum-based drugs. RNA-Seq analysis identified dysregulation in hypoxia, immune response, and metabolic pathways .
Mechanistic Insights: FBXL17 modulates epithelial-to-mesenchymal transition (EMT) and iron homeostasis, suggesting its role in metastasis .
SCF Complex Role: FBXL17 participates in substrate recognition for ubiquitination, akin to FBXL19 (a homolog), which targets Rac3 for proteasomal degradation .
Structural Analysis: The F-box domain enables interaction with SKP1, while leucine-rich repeats (LRRs) mediate substrate binding .
Western Blot: Detects endogenous FBXL17 at ~72 kDa in HeLa, MCF-7, and HepG2 lysates .
Immunohistochemistry: Strong staining in human kidney and brain tissues, confirming tissue-specific expression .
Cross-Reactivity: No observed cross-reactivity with Rac1 or other F-box proteins (e.g., FBXL18, FBXL19) .