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The molecular mechanisms governing γ‐secretase cleavage specificity are not fully understood. Herein, we demonstrate that extending the transmembrane domain of the amyloid precursor protein‐derived C99 substrate in proximity to the cytosolic face strongly influences γ–secretase cleavage specificity. Sequential insertion of leucines or replacement of membrane‐anchoring lysines by leucines elevated...
The eukaryotic translation initiation factor eIF4E is a potent oncogene that promotes the nuclear export and translation of specific transcripts. Here, we have discovered that eIF4E alters the cytoplasmic face of the nuclear pore complex (NPC), which leads to enhanced mRNA export of eIF4E target mRNAs. Specifically, eIF4E substantially reduces the major component of the cytoplasmic fibrils of the...
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