title: Characterization of FBX25, encoding a novel brain-expressed F-box protein.
abstract: F-box proteins (FBPs) confer substrate specificity to the SCF-type (Skp1/Cul1/FBP) of ubiquitin ligase complexes through their F-box. Multiple FBPs have been predicted, but experimental evidence is lagging. We report on the predicted human FBP hFBX25 which we found to be disrupted in a mentally retarded translocation carrier suffering from epileptic seizures. We investigated hFBX25's genomic organization and established hFBX25 as an FBP by verifying its interaction with Skp1 and Cul1. In the process, we identified an atypical serine residue in the F-box which is crucial for the hFBX25-Skp1 binding. We determined hFBX25's subcellular localization. We found strong transcription in human brain. In mouse embryonic sections, mFbx25 shows predominantly neuronal expression and in adult mouse brain, expression is confined to the hippocampus, the cerebral cortex and the Purkinje cell layer. Interestingly, aberrations in the ubiquitin pathway have been linked to neurological conditions.
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Human Molecular Genetics, Ihnestr. 73, D-14195 Berlin, Germany.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hagens
authors.forename: Eleonora
authors.initials: E
authors.lastname: Minina
authors.forename: Susann
authors.initials: S
authors.lastname: Schweiger
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Vera
authors.initials: V
authors.lastname: Kalscheuer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001923:Brain Chemistry; D018797:Cell Cycle Proteins / Q000378:metabolism; D044842:Cullin Proteins / Q000378:metabolism; D044783:F-Box Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D040461:Gene Components; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D012694:Serine; D013379:Substrate Specificity; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D044783:F-Box Proteins; C510759:FBXO25 protein, human; D009419:Nerve Tissue Proteins; D044786:S-Phase Kinase-Associated Proteins; D012694:Serine