A Novel F Box Protein, NFB42, Is Highly Enriched in Neurons and Induces Growth Arrest

Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination

“…1c). We isolated six positives from 120,000 clones, and all six independently encoded Fbx2, a component of E3 ubiquitin ligase (16).…”

“…Fbx2͞NFB42͞Fbs1 is a neuron-specific F-box protein that recognizes N-linked high-mannose oligosaccharides on substrate proteins (16,17). Because mannose modifications occur in the lumen of the endoplasmic reticulum (ER), Fbx2 must recognize substrates after their retrotranslocation from the ER as part of the ER degradation (ERAD) pathway (18).…”

Cloning and Characterization of a Novel Oocyte-Specific Gene Encoding an F-Box Protein in Rainbow Trout (Oncorhynchus mykiss).

“…Our results also show that the expression of fbxoo mRNA and protein is detected in both cytoplasm and nucleus of oocyte at early developmental stages. While many F-box proteins are ubiquitously expressed [25], tissue specific F-box proteins with specific functions have been reported [26][27][28]. In particular, muscle-specific F-box proteins such as ATROGIN-1 and MURF1 are known to have unique functions in the degradation of important regulatory proteins during muscle atrophy [27,29].…”

FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest

“…[22][23][24][25][26][27] In previous studies, we found that overexpressing FBG1 in CHO cells resulted in growth arrest. 28 We and others also previously showed that FBG1 had a relatively low affinity for the SCF scaffold protein Cul1; in fact, rather than forming the canonical SCF complex, FBG1 primarily formed a dimer with Skp1. 22,23,[29][30][31][32] Finally we found that FBG1-mediated growth arrest required an intact F box, suggesting that the growth arrest may be mediated through the FBG1-Skp1 interaction.…”

“…In an earlier study, we showed that FBG1 overexpression caused a growth arrest in CHO cells. 28 To determine whether this effect was a consequence of APC2 binding via its D box, we overexpressed wild-type FBG1 and the BD and 27D mutants (Fig. 10) in Cos7 cells, assaying for growth arrest by cell counts 24-72 hours later.…”