title: Nuclear spheres modulate the expression of BEST1 and GADD45G.
abstract: Nuclear spheres are composed of FE65, TIP60, BLM and other yet unknown proteins. The amyloid precursor protein plays a central role for the generation of these highly toxic aggregates in the nucleus of cells. Thus, nuclear spheres might play a crucial role in Alzheimer's disease (AD). However, studies are hampered by the elevated cell death, once spheres are generated. In this work, we established for the first time a stable nuclear sphere model based on the inductive expression of FE65 and TIP60 following Doxycycline stimulation. We studied hitherto controversially discussed target genes, give clues for the reason of controversy, and moreover report new highly reliable targets bestrophin 1 and growth arrest and DNA-damage-inducible protein gamma. qPCR studies further revealed that the regulation of these targets strongly depends on the generation of nuclear spheres, but not on the induction of FE65 or TIP60 alone. As the bestrophin 1 ion channel was recently described to be involved in the abnormal release of GABA, our study might reveal the missing link between AD associated neurotransmitter changes and the amyloid precursor protein.
authors.affiliation: Cell Signaling in Neurodegeneration (CSIN), Medical Proteome-Center, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Loosse
authors.affiliation: Cell Signaling in Neurodegeneration (CSIN), Medical Proteome-Center, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Pawlas
authors.affiliation: Cell Signaling in Neurodegeneration (CSIN), Medical Proteome-Center, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Hassan S S
authors.initials: HS
authors.lastname: Bukhari
authors.affiliation: Department of Molecular GI-Oncology, Clinical Research Center, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Abdelouahid
authors.initials: A
authors.lastname: Maghnouj
authors.affiliation: Department of Molecular GI-Oncology, Clinical Research Center, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Functional Proteomics, Medical Proteome-Center, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Marcus
authors.affiliation: Cell Signaling in Neurodegeneration (CSIN), Medical Proteome-Center, Ruhr-University Bochum, 44801 Bochum, Germany. Electronic address: thorsten.t.mueller@rub.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Müller
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000075002:Bestrophins; D002467:Cell Nucleus / Q000378:metabolism*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000074443:Lysine Acetyltransferase 5; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D051548:Histone Acetyltransferases; D047908:Intracellular Signaling Peptides and Proteins; D000074443:Lysine Acetyltransferase 5; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C113133:BEST1 protein, human; C485654:GADD45G protein, human; D000097642:GADD45 Proteins; C098489:KAT5 protein, human
keywords: BEST1; FE65/TIP60 inducible cell line; GADD45G; Nuclear spheres; STMND1