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

• Published in: Neurobiology of aging 2009-12, Vol.30 (12), p.1962-1974
• Main Authors: Broytman, Oleg, Westmark, Pamela R, Gurel, Zafer, Malter, James S
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; 3′-UTR regulatory elements; Alzheimer's disease; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Binding Sites; Biological and medical sciences; Cell Line, Tumor; DEAD-box RNA Helicases - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Electrophoresis, Polyacrylamide Gel; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Immunoblotting; Immunohistochemistry; Immunoprecipitation; Internal Medicine; Mass Spectrometry; Medical sciences; Microscopy, Confocal; Neurology; Neurons - metabolism; Protease Nexins; Protein Multimerization; Proto-Oncogene Proteins - metabolism; rck/p54; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA, Messenger - metabolism; Transfection; Vertebrates: nervous system and sense organs; β-Amyloid precursor protein
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2008.02.011

Abstract Overproduction of amyloid precursor protein (APP) and β-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.