title: The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation.
abstract: Lamin A is a component of the nuclear matrix that also controls proliferation by largely unknown mechanisms. NF-Y is a ubiquitous protein involved in cell proliferation composed of three subunits (-YA -YB -YC) all required for the DNA binding and transactivation activity. To get clues on new NF-Y partner(s) we performed a mass spectrometry screening of proteins that co-precipitate with the regulatory subunit of the complex, NF-YA. By this screening we identified lamin A as a novel putative NF-Y interactor. Co-immunoprecipitation experiments and confocal analysis confirmed the interaction between the two endogenous proteins. Interestingly, this association occurs on euchromatin regions, too. ChIP experiments demonstrate lamin A enrichment in several promoter regions of cell cycle related genes in a NF-Y dependent manner. Gain and loss of function experiments reveal that lamin A counteracts NF-Y transcriptional activity. Taking advantage of a recently generated transgenic reporter mouse, called MITO-Luc, in which an NF-Y-dependent promoter controls luciferase expression, we demonstrate that lamin A counteracts NF-Y transcriptional activity not only in culture cells but also in living animals. Altogether, our data demonstrate the occurrence of lamin A/NF-Y interaction and suggest a possible role of this protein complex in regulation of NF-Y function in cell proliferation.
authors: Department of Research, Advanced Diagnostics and Technological Innovation, SAFU Unit, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors: Lucia
authors: L
authors: Cicchillitti
authors: Department of Research, Advanced Diagnostics and Technological Innovation, SAFU Unit, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors: Isabella
authors: I
authors: Manni
authors: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Department of Epidemiology and Preclinical Research, 00149 Rome, Italy.|Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
authors: Carmine
authors: C
authors: Mancone
authors: Department of Research, Advanced Diagnostics and Technological Innovation, Genomic and Epigenetic Unit, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.
authors: Giulia
authors: G
authors: Regazzo
authors: Department of Research, Advanced Diagnostics and Technological Innovation, Genomic and Epigenetic Unit, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.
authors: Manuela
authors: M
authors: Spagnuolo
authors: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Department of Epidemiology and Preclinical Research, 00149 Rome, Italy.
authors: Tonino
authors: T
authors: Alonzi
authors: Fondazione Luigi Maria Monti, Istituto Dermopatico dell'Immacolata-IRCCS, Laboratorio di Patologia Vascolare, 00167 Rome, Italy.
authors: Fabrizio
authors: F
authors: Carlomosti
authors: Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, 00144 Rome, Italy.
authors: Maria Lucia
authors: ML
authors: Dell'Anna
authors: Department of Oncology and Hemato-Oncology and Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
authors: Giulia
authors: G
authors: Dell'Omo
authors: Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Via Elio Chianesi 53, 00144, Rome, Italy.
authors: Mauro
authors: M
authors: Picardo
authors: Center of Excellence on Neurodegenerative Diseases, Department of Oncology and Hemato-Oncology, University of Milan, 20133 Milan, Italy.
authors: Paolo
authors: P
authors: Ciana
authors: Fondazione Luigi Maria Monti, Istituto Dermopatico dell'Immacolata-IRCCS, Laboratorio di Patologia Vascolare, Via dei Monti di Creta 104, Rome 00167, Italy Rome, Italy.
authors: Maurizio C
authors: MC
authors: Capogrossi
authors: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Department of Epidemiology and Preclinical Research, 00149 Rome, Italy.|Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
authors: Marco
authors: M
authors: Tripodi
authors: Fondazione Luigi Maria Monti, Istituto Dermopatico dell'Immacolata-IRCCS, Laboratorio di Patologia Vascolare, Via dei Monti di Creta 104, Rome 00167, Italy Rome, Italy.
authors: Alessandra
authors: A
authors: Magenta
authors: Department of Research, Advanced Diagnostics and Technological Innovation, Genomic and Epigenetic Unit, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.
authors: Maria Giulia
authors: MG
authors: Rizzo
authors: Department of Research, Advanced Diagnostics and Technological Innovation, SAFU Unit, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors: Aymone
authors: A
authors: Gurtner
authors: Department of Research, Advanced Diagnostics and Technological Innovation, SAFU Unit, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors: Giulia
authors: G
authors: Piaggio
mesh_terms: D000818:Animals; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D020218:Response Elements; D014158:Transcription, Genetic
chemical_list: D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D046912:Multiprotein Complexes
keywords: cell cycle; euchromatin; nuclear lamina; proliferation; transcription