The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation
| Autor: | Giulia Regazzo, Paolo Ciana, Aymone Gurtner, Maurizio C. Capogrossi, Lucia Cicchillitti, Carmine Mancone, Manuela Spagnuolo, Marco Tripodi, Fabrizio Carlomosti, Giulia Dell'Omo, Maria Lucia Dell'Anna, Tonino Alonzi, Giulia Piaggio, Isabella Manni, Mauro Picardo, Alessandra Magenta, Maria Giulia Rizzo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chromatin Immunoprecipitation Euchromatin Transcription Genetic Proliferation Mice Transgenic Biology Cell cycle Response Elements 03 medical and health sciences Mice Cell Line Tumor Animals Humans Promoter Regions Genetic Cell Proliferation Nuclear lamina Transcription Oncology Genetics Regulation of gene expression Transcriptional activity CCAAT-Binding-Factor Cell growth High-Throughput Nucleotide Sequencing Lamin Type A humanities DNA-Binding Proteins Protein Transport 030104 developmental biology CCAAT-Binding Factor Gene Expression Regulation Multiprotein Complexes Lamin Research Paper Protein Binding |
| Zdroj: | Oncotarget Oncotarget 8 (2017): 2628–2646. doi:10.18632/oncotarget.12914 info:cnr-pdr/source/autori:Cicchillitti, Lucia; Manni, Isabella; Mancone, Carmine; Regazzo, Giulia; Spagnuolo, Manuela; Alonzi, Tonino; Carlomosti, Fabrizio; Dell'Anna, Maria Lucia; Dell'Omo, Giulia; Picardo, Mauro; Ciana, Paolo; Capogrossi, Maurizio C.; Tripodi, Marco; Magenta, Alessandra; Rizzo, Maria Giulia; Gurtner, Aymone; Piaggio, Giulia/titolo:The laminA%2FNF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation/doi:10.18632%2Foncotarget.12914/rivista:Oncotarget/anno:2017/pagina_da:2628/pagina_a:2646/intervallo_pagine:2628–2646/volume:8 |
| Popis: | // Lucia Cicchillitti 1, * , Isabella Manni 1, * , Carmine Mancone 2, 3 , Giulia Regazzo 4 , Manuela Spagnuolo 4 , Tonino Alonzi 2 , Fabrizio Carlomosti 5, † , Maria Lucia Dell’Anna 6 , Giulia Dell’Omo 7 , Mauro Picardo 6 , Paolo Ciana 8 , Maurizio C. Capogrossi 5 , Marco Tripodi 2, 3 , Alessandra Magenta 5 , Maria Giulia Rizzo 4 , Aymone Gurtner 1, # , Giulia Piaggio 1, # 1 Department of Research, Advanced Diagnostics and Technological Innovation, SAFU Unit, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy 2 National Institute for Infectious Diseases L. Spallanzani, IRCCS, Department of Epidemiology and Preclinical Research, 00149 Rome, Italy 3 Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy 4 Department of Research, Advanced Diagnostics and Technological Innovation, Genomic and Epigenetic Unit, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy 5 Fondazione Luigi Maria Monti, Istituto Dermopatico dell’Immacolata-IRCCS, Laboratorio di Patologia Vascolare, 00167 Rome, Italy 6 Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, 00144 Rome, Italy 7 Department of Oncology and Hemato-Oncology and Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy 8 Center of Excellence on Neurodegenerative Diseases, Department of Oncology and Hemato-Oncology, University of Milan, 20133 Milan, Italy * These authors have contributed equally to this work # Co-last authors † In memory of Fabrizio Carlomosti who tragically passed away on October the 29 th 2015 Correspondence to: Giulia Piaggio, email: piaggio@ifo.it Aymone Gurtner, email: gurtner@ifo.it Keywords: transcription, proliferation, cell cycle, euchromatin, nuclear lamina Received: May 18, 2016 Accepted: October 10, 2016 Published: October 26, 2016 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|