title: ATBF1 is a novel amyloid-β protein precursor (AβPP) binding protein that affects AβPP expression.
abstract: The cytoplasmic C-terminal domain of amyloid-β protein precursor (AβPP) binds to several proteins that regulate the trafficking and processing of AβPP and affects amyloid-β (Aβ) production. We previously reported that levels of AT-motif binding factor 1 (ATBF1) are increased in the brains of 17-month-old Tg2576 mice compared with wild-type controls, and that Aβ42 increases ATBF1 expression, inducing death in primary rat cortical neurons. Here, we show that ATBF1 levels are increased in the cytoplasm of hippocampal neurons in Alzheimer's disease (AD) brains compared with non-AD brains. Furthermore, cotransfection of human embryonic kidney (HEK293T) and human neuroblastoma (SH-SY5Y) cells with ATBF1 and AβPP695 increased steady-state levels of AβPP via the binding of ATBF1 to the AβPP cytoplasmic domain (amino acids 666-690), resulting in increased Aβ production and cellular and soluble AβPP (sAβPP) levels without affecting the activity or levels of AβPP processing enzymes (α-, β-, or γ-secretase). Conversely, knockdown of endogenous ATBF1 reduced levels of cellular AβPP, sAβPP, and Aβ in HEK293 cells overexpressing human AβPP695. Our findings provide insight into the dynamics of AβPP processing and Aβ production, and suggest that ATBF1 is a novel AβPP binding protein that may be a suitable therapeutic target for AD.
authors: Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG), Morioka, Obu, Aichi, Japan.
authors: Kyung-Ok
authors: KO
authors: Uhm
authors: Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG), Morioka, Obu, Aichi, Japan.
authors: Mi-Jeong
authors: MJ
authors: Kim
authors: Department of Pathology, Niigata Rosai Hospital, Niigata, Japan.
authors: Makoto
authors: M
authors: Kawaguchi
authors: Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan Department of Community-based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Hiroyasu
authors: H
authors: Akatsu
authors: Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Yutaka
authors: Y
authors: Miura
authors: Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Sachiyo
authors: S
authors: Misumi
authors: Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Hideki
authors: H
authors: Hida
authors: Laboratory of Cellular Aging and Neurodegeneration, Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Korea.
authors: Eun-Kyoung
authors: EK
authors: Choi
authors: Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Korea.
authors: Yong-Sun
authors: YS
authors: Kim
authors: Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Makoto
authors: M
authors: Michikawa
authors: Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology (NCGG), Morioka, Obu, Aichi, Japan Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Cha-Gyun
authors: CG
authors: Jung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018398:Homeodomain Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C071660:ZFHX3 protein, human
keywords: ATBF1; Alzheimer's disease; Aβ production; AβPP binding protein; AβPP stabilization