title: 3'poly-G-tailed ODNs inhibit F-spondin to induce cell death and neurite retraction in rat embryonic neurons.
abstract: The effects and mechanism of action of oligodeoxyribonucleotides containing CpG motif (CpG-ODNs) on neuron cells are largely unexamined. Here, we found that CpG-A ODNs but not other types of CpG-ODNs induced neurite retraction and cell apoptosis of rat embryonic neurons in a TLR9-independent manner. These effects of CpG-A ODNs were primarily due to the poly-guanosine at the 3' terminus (3'G-ODNs). Pull-down analysis showed that 3'G-ODNs associated with transcription factor Y-BOX1 (YB-1) to facilitate the translocation of YB-1 into the nucleus via the nuclear localizing sequence of YB-1. YB-1 then interacted with the promoter of F-spondin directly at -45 and -1,375 sites as demonstrated by chromatin immunoprecipitation (ChIP) analysis. Binding of YB-1 to F-spondin promoter resulted in downregulation of F-spondin expression. Overexpression of F-spondin rescued the cell death and neurite retraction induced by 3'G-ODNs in embryonic neuron cells. Taken together, these findings suggest that 3'G-ODNs enhance nucleus YB-1 to inhibit F-spondin leading to cell death and neurite retraction of embryonic neuron cells.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Cheng
authors.forename: Tai-An
authors.initials: TA
authors.lastname: Chen
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liang
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Liang
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002853:Chromatography, Liquid; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D013058:Mass Spectrometry; D050505:Mutant Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D019913:Nuclear Localization Signals; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011068:Poly G / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D036341:Intercellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D019913:Nuclear Localization Signals; D009838:Oligodeoxyribonucleotides; D010455:Peptides; C498955:Spon1 protein, rat; D051217:Toll-Like Receptor 9; D051840:Y-Box-Binding Protein 1; D011068:Poly G; D053148:Caspase 3; D053179:Caspase 7