Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS
| Autor: | Andrea Urbani, Claudia Cericola, Daniela Corda, Andrea R. Beccari, Maurizio Ronci, Prisca Liberali, Marco Nardini, Martino Bolognesi, Vasiliki S. Lalioti, Giuliana Catara, Carmen Valente, Agostino Bruno, Antonino Colanzi, Antonio De Flora, Alberto Luini, Giovanna Grimaldi |
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| Přispěvatelé: | National Institutes of Health (US), Associazione Italiana per la Ricerca sul Cancro, Colanzi, Antonino, Grimaldi, Giovanna, Catara, Giuliana, Valente, Carmen, Cericola, Claudia, Liberali, Prisca, Ronci, Maurizio, Lalioti, Vasiliki S, Bruno, Agostino, Beccari, Andrea R, Urbani, Andrea, De Flora, Antonio, Nardini, Marco, Bolognesi, Martino, Luini, Alberto, Corda, Daniela |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular anticancer molecules chemistry.chemical_compound Cytosol Membrane fission Competitive Models Multidisciplinary Membrane Glycoproteins Blotting Settore BIO/12 Cell cycle Brefeldin A Biological Sciences Cell biology DNA-Binding Proteins ADP-ribosylation symbols mitosis Animals HeLa Cells Humans Protein Processing Post-Translational Alcohol Oxidoreductases Antigens CD38 Protein Binding Binding Sites Rats ADP-ribosyl Cyclase Blotting Western NAD cell signaling Golgi fragmentation Binding Competitive Protein Structure Tertiary Adenosine Diphosphate Ribose Western Intracellular Protein Structure Biology symbols.namesake Antigens Mitosis Protein Processing Post-Translational Molecular Golgi apparatus Binding ADP-ribosyl Cyclase 1 chemistry CD38 Tertiary |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America 110 (2013): 9794–9799. doi:10.1073/pnas.1222413110. info:cnr-pdr/source/autori:Colanzi A, Grimaldi G, Catara G, Valente C, Cericola C, Liberali P, Ronci M, Lalioti VS, Bruno A, Beccari AR, Urbani A, De Flora A, Nardini M, Bolognesi M, Luini A, Corda D./titolo:Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1%2FBARS./doi:10.1073%2Fpnas.1222413110./rivista:Proceedings of the National Academy of Sciences of the United States of America/anno:2013/pagina_da:9794/pagina_a:9799/intervallo_pagine:9794–9799/volume:110 Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0027-8424 |
| Popis: | ADP-ribosylation is a posttranslational modification that modulates the functions of many target proteins. We previously showed that the fungal toxin brefeldin A (BFA) induces the ADP-ribosylation of C-terminal-binding protein-1 short-form/BFA-ADP-ribosylation substrate (CtBP1-S/BARS), a bifunctional protein with roles in the nucleus as a transcription factor and in the cytosol as a regulator of membrane fission during intracellular trafficking and mitotic partitioning of the Golgi complex. Here, we report that ADP-ribosylation of CtBP1-S/BARS by BFA occurs via a nonconventional mechanism that comprises two steps: (i) synthesis of a BFA-ADP-ribose conjugate by the ADP-ribosyl cyclase CD38 and (ii) covalent binding of the BFA-ADP-ribose conjugate into the CtBP1-S/BARS NAD+-binding pocket. This results in the locking of CtBP1-S/BARS in a dimeric conformation, which prevents its binding to interactors known to be involved in membrane fission and, hence, in the inhibition of the fission machinery involved in mitotic Golgi partitioning. As this inhibition may lead to arrest of the cell cycle in G2, these findings provide a strategy for the design of pharmacological blockers of cell cycle in tumor cells that express high levels of CD38. We thank all colleagues who kindly provided antibodies and reagents; Dr. J. Donaldson (National Institutes of Health) for BFA analogs; Dr. C. P. Berrie for editorial assistance; and Drs. C. Limina, A. Tamburro, M. G. Silletta, R. Weigert, and S. Spanò (Negri Sud Institute) for performing initial experiments. We also acknowledge financial support from Italian Association for Cancer Research (AIRC) through the Grants IG4664 and IG10341 (to D.C.), IG4700 (to A.L.), and IG6074 (to A.C.); and from the Liguria Region and the Ministry of Education, University, and Research (Fund for Investments in Basic Research Project; A.D.F.). G.G. and C.V. received fellowships from AIRC (Italian Foundation for Cancer Research). Financial support from Technological Innovation Fund DM 24/09/2009, Legge 46/82-MEF, and Project FaReBio di Qualità also is acknowledged |
| Databáze: | OpenAIRE |
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