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.
Broytman
Oleg
O
Department of Pathology and Laboratory Medicine, Neuroscience Training Program, Waisman Center for Developmental Disabilities and Institute on Aging, University of Wisconsin, Madison, 1500 Highland Avenue, Madison, WI 53705, USA.
Westmark
Pamela R
PR
Gurel
Zafer
Z
Malter
James S
JS
D020413:3' Untranslated Regions; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism*; D058255:Protease Nexins; D055503:Protein Multimerization; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D020413:3' Untranslated Regions; C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D058255:Protease Nexins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases