Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions(614 views) Fantini D, Vascotto C, Marasco D, D'Ambrosio C, Romanello M, Vitagliano L, Pedone C, Poletto M, Cesaratto L, Quadrifoglio F, Scaloni A, Radicella JP, Tell G
Keywords: Apurinic Apyrimidinic Endonuclease 1, Dna (apurinic Or Apyrimidinic Site) Lyase, Lysine, Nucleophosmin, Recombinant Protein, Unclassified Drug, Acetylation, Amino Acid Sequence, Amino Terminal Sequence, Article, Cell Culture, Controlled Study, Enzyme Regulation, Excision Repair, Gel Mobility Shift Assay, Human, Human Cell, In Vivo Study, Nonhuman, Nucleotide Sequence, Peptide Mapping, Peptide Synthesis, Phylogeny, Plasmid, Polymerase Chain Reaction, Priority Journal, Protein Expression, Protein Processing, Protein Protein Interaction, Rna Binding, Rna Metabolism, Surface Plasmon Resonance, Transient Transfection, Western Blotting, Binding Sites, Dna-(apurinic Or Apyrimidinic Site) Lyase, Hela Cells, Molecular Sequence Data, Protein Structure, Tertiary, Sequence Analysis, Mammalia, Chemistry, Classification,
Affiliations: *** IBB - CNR ***
Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy.
Department of Biological Sciences, University of Naples 'Federico II', Belarus
Institute of Biostructures and Bioimaging, National Research Council, 80134 Naples, Italy
Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Naples, Italy
CEA, Institut de Radiobiologie Cellulaire et Moléculaire, UMR217 CNRS, F-92265 Fontenay-aux-Roses, France
References: Not available.
Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions
Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is involved in base excision DNA repair (BER) and in regulation of gene expression, acting as a redox co-activator of several transcription factors. Recent findings highlight a novel role for APE1 in RNA metabolism, which is modulated by nucleophosmin (NPM1). The results reported in this article show that five lysine residues (K24, K25, K27, K31 and K32), located in the APE1 N-terminal unstructured domain, are involved in the interaction of APE1 with both RNA and NPM1, thus supporting a competitive binding mechanism. Data from kinetic experiments demonstrate that the APE1 N-terminal domain also serves as a device for fine regulation of protein catalytic activity on abasic DNA. Interestingly, some of these critical lysine residues undergo acetylation in vivo. These results suggest that protein-protein interactions and/or post-translational modifications involving APE1 N-terminal domain may play important in vivo roles, in better coordinating and fine-tuning protein BER activity and function on RNA metabolism.
Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(451 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote