SCF-FBXL17 E3 ubiquitin ligase complex (SCF-FBXL17)

The SCF-FBXL17 E3 ubiquitin ligase complex, also known as the Dimerization Quality Control (DQC) ligase, is a specialized protein degradation machine that monitors the assembly of BTB (Broad-complex, Tramtrack, and Bric-à-brac) domain-containing proteins. BTB proteins typically function as homodimers to regulate critical cellular processes like stress responses and development; however, they are prone to forming inactive heterodimers due to the high conservation of their dimerization interface. SCF-FBXL17 specifically recognizes these aberrant heterodimers or mutant homodimers by probing the shape and complementarity of the BTB interface, subsequently ubiquitylating the "incorrect" subunits to trigger their proteasomal clearance. This quality control mechanism is essential for proper neural crest development and neuronal survival, and its dysregulation is linked to various cancers and neurodegenerative diseases. In oncology, SCF-FBXL17 regulates the levels of key transcription factors like BACH1 and SUFU, making it an attractive target for therapeutic modulation or as a recruitment module for targeted protein degradation (PROTAC) strategies. Small molecules like quercetin have been investigated in silico for their ability to bind the DQC catalytic site, suggesting potential for future drug development.

Other names

Dimerization quality control E3 ligaseDQC ubiquitin ligaseFBXL17F-box/LRR-repeat protein 17

The SCF-FBXL17 complex acts as a dimerization quality control (DQC) E3 ligase that selectively recognizes and ubiquitylates aberrant or inactive BTB domain-containing dimers (such as heterodimers or mutant homodimers) for proteasomal degradation, thereby ensuring the integrity of BTB-mediated signaling pathways.