Targeting Nuclear Import Shuttles, Importins/Karyopherins alpha by a Peptide Mimicking the NFjB1/p50 Nuclear Localization Sequence

Background-—We recently reported that a bifunctional nuclear transport modifier (NTM), cSN50.1 peptide, reduced atherosclerosis, plasma cholesterol, triglycerides, and glucose along with liver fat and inflammatory markers, in a murine model of familial hypercholesterolemia. We determined that cSN50.1 improved lipid homeostasis by modulating nuclear transport of sterol regulatory element-binding proteins through interaction with importin b. Previous studies established that cSN50.1 and related NTMs also modulate nuclear transport of proinflammatory transcription factors mediated by binding of their nuclear localization sequences (NLSs) to importins/karyopherins a. However, selectivity and specificity of NTMs for importins/karyopherins a were undetermined.