Rck/p54 interacts with APP mRNA as part of a multi-protein complex and enhances APP mRNA and protein expression in neuronal cell lines

Overproduction of amyloid precursor protein (APP) and beta-amyloid likely contribute to neurodegeneration seen in Alzheimer's disease (AD). APP mRNA contains several, 3'-untranslated region (UTR), cis-acting regulatory elements. A 52 base element (52sce), immediately downstream from the stop codon, has been previously shown to complex with uncharacterized cytoplasmic proteins. In this study, we purify and identify six proteins that specifically bind to the 52sce, and show that these proteins interact with each other and with APP mRNA in intact human neuroblastoma cells. We also present evidence that at least one of these proteins, the DEAD-box helicase rck/p54, is involved in post-transcriptional regulation, as its Overexpression in cultured cells results in elevated levels of APP mRNA and protein. These findings suggest a novel mechanism for post-transcriptional regulation of APP mRNA. (C) 2008 Elsevier Inc. All rights reserved.