title: Structural and biological function of NYD-SP15 as a new member of cytidine deaminases.
abstract: Recent studies were mainly focus on the cytidine deaminase family genes, which contained a lot of members that varied on the function of catalytic deamination in RNA or DNA and were involved in the process of growth maintenance, host immunity, retroviral infection, tumorigenesis, and drug resistance with a feature of C-U deamination. In this study, we identified a new member of cytidine deaminase family, NYD-SP15. Previous work showed that the deduced structure of the protein contained two dCMP_cyt_deam domains, which were involved in zinc ion binding. NYD-SP15 was expressed variably in a wide range of tissues, indicating its worthy biological function and creative significances. Sequence analysis, RT-PCR, western blot, flow cytometry, direct-site mutation and GST pull-down assay were performed to analyze the construction and function of NYD-SP15. The results in our studies showed that NYD-SP15 was closely related to deoxycytidylate deaminase and cytidine deaminase, with authentic cytidine deaminase activity in vivo and vitro as well as homo dimerization effects. NYD-SP15 contained nuclear localization sequence (NLS) and nuclear export-signal (NES) and could dynamically shuttle between the nucleus and cytoplasm. Furthermore, NYD-SP15 gene over-expression reduced the cells growth and blocked G1 to S phase, which implied a potential inhibition effect on cell growth.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Basic Medical Sciences of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: JIANMINLI@yeah.net.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qinghuai
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003564:Cytidine Deaminase / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D009154:Mutation; D019913:Nuclear Localization Signals; D010802:Phylogeny; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C520503:CDADC1 protein, human; D029968:Escherichia coli Proteins; D019913:Nuclear Localization Signals; D014157:Transcription Factors; C540081:rpoB protein, E coli; D012321:DNA-Directed RNA Polymerases; D003564:Cytidine Deaminase
keywords: Cell inhibition; Cytidine deaminase; NYD-SP15; Shuttling mechanism; Subcellular localization