RanBP9 modulates AICD localization and transcriptional activity via direct interaction with Tip60.

摘要: Proteolytic processing of the amyloid-β protein precursor (AβPP) occurs via alternative pathways, culminating with production AβPP intracellular domain (AICD). AICD can translocate to nucleus and regulate transcription, but its activity is modulated by interactions other proteins. In nucleus, AICD, FE65, Tip60 associate into AFT complexes, which are targeted nuclear spots correspond transcription factories. Here we report that RanBP9 interacts cytoplasmic AβPP, through NPXY internalization motif. Moreover, interaction also described. The RanBP9-Tip60 dramatically relocated from a widespread cellular distribution speckles. central aspect in determining protein's function resulting proteolytic fragments, among them AICD. latter results amyloidogenic pathway peptidic species predominantly involved signaling. Of note transfection was previously demonstrated increase generation. show relocates Tip60-enriched speckles, prevented formation formation, having therefore negative effect on mediated signaling consequently complex formation. Furthermore, transfecting cells increasing amounts RanBP9, expression AICD-regulated genes, including itself, reduced. Given data presented, one deduce has an inhibitory regulatory AICD-mediated relocating away