Disease relevance of FBXO2

• Replication-initiator protein (UL9) of the herpes simplex virus 1 binds NFB42 and is degraded via the ubiquitin-proteasome pathway [1].
• In an initial attempt to characterize the function of this protein, NFB42 was transfected into N1E-115 neuroblastoma and Chinese hamster ovary cells [2].
• We have now found that HSV-1 infection promotes the shuttling of NFB42 between the cytosol and the nucleus in both 293T cells and primary hippocampal neurons, permitting NFB42 to bind to the phosphorylated UL9 protein, which is localized in the nucleus [3].

High impact information on FBXO2

• Pre-integrin beta 1 is a target of Fbx2; these two proteins interact in the cytosol after inhibition of the proteasome [4].
• In addition, expression of the mutant Fbx2 Delta F, which lacks the F-box domain that is essential for forming the SCF complex, appreciably blocks degradation of typical substrates of the ER-associated degradation pathway [4].
• CHIP facilitates the ubiquitination and degradation of Fbx2-bound glycoproteins, including unassembled NMDA receptor subunits [5].
• These findings indicate that CHIP acts with Fbx2 in a novel ubiquitination pathway that links CHIP to glycoprotein quality control in neurons [5].
• Here we show that Fbx2, a brain-enriched F-box protein implicated in the ubiquitination of glycoproteins discarded from the endoplasmic reticulum, binds the co-chaperone/ubiquitin ligase CHIP (C terminus of Hsc-70-interacting protein) through a unique N-terminal PEST domain in Fbx2 [5].

Biological context of FBXO2

• The presence of an F box in NFB42 suggests that it may be involved in cell cycle regulation; however, its expression in postmitotic neurons indicates that it is not involved in regulating typical cell cycle events [2].
• In addition, we have evaluated the effect of hFbg on two functional events related to expression and resolution of inflammation: cytotoxic capacity and rate of neutrophil apoptosis [6].
• Ectopic expression of NFB42 both suppressed the formation of aggresome-like structures and the phosphorylation of the translational regulator eIF2alpha induced by overproduction of SHPS-1 as well as increased the amount of mature SHPS-1 at the cell surface [7].

Anatomical context of FBXO2

• The expression of full-length NFB42, but not an F box deletion mutant, inhibits proliferation in both cell lines [2].
• We have now shown that incubation of purified neutrophils with hFbg induces a transient and rapid elevation of free intracellular Ca2+ [6].

Associations of FBXO2 with chemical compounds

• These analyses revealed that Man(3)GlcNAc(2) had the strongest affinity and the chitobiose and alpha1-->6 linked Man residue are necessary for Fbs1 to recognize a sugar [8].

Other interactions of FBXO2

• Although OCP1 displays extensive homology to an F-box protein recently cloned from rat brain (NFB42), clustered sequence non-identities indicate that the two proteins are transcribed from distinct genes [9].

References