TY - JOUR
T1 - Rck/p54 interacts with APP mRNA as part of a multi-protein complex and enhances APP mRNA and protein expression in neuronal cell lines
AU - Broytman, Oleg
AU - Westmark, Pamela R.
AU - Gurel, Zafer
AU - Malter, James S.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants R01 AG10675 and P30 HD03352 (to J.S.M.), and by a private donation by William and Jean Roper (to the Waisman Center). We are indebted to Dr. Thomas Gelehrter (University of Michigan Medical School) for the generous gift of the anti-PAI-RBP1 polyclonal antibody, Dr. Ger J. M. Pruijn (Katholieke Universiteit Nijmegen, Nijmegen, Netherlands) for the gift of the SW1, SW3, and SW5.8 anti-La/SS-B monoclonal antibodies, and Dr. Yukihiro Akao (Gifu International Institute of Biotechnology, Gifu, Japan) for the gift of the anti-rck/p54 polyclonal antibody. We also wish to thank them for providing the respective immunoprecipitation and immunoblot protocols. We thank Dr. Mary Ann Gawinowicz (Columbia University Protein Core and DNA Sequencing Facility, Columbia University, New York, NY) for MALDI-MS peptide mass mapping, Dr. Cara Westmark for training in real-time PCR and the immunoprecipitation/RNA extraction protocol, and Drs. Janet Mertz and Jeffrey Ross for advice in experimental design.
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - 3′-UTR regulatory elements
KW - Alzheimer's disease
KW - rck/p54
KW - β-Amyloid precursor protein
UR - http://www.scopus.com/inward/record.url?scp=70349984421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349984421&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2008.02.011
DO - 10.1016/j.neurobiolaging.2008.02.011
M3 - Article
C2 - 18378046
AN - SCOPUS:70349984421
SN - 0197-4580
VL - 30
SP - 1962
EP - 1974
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 12
ER -