Oncotarget

Research Papers:

The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation

Lucia Cicchillitti, Isabella Manni, Carmine Mancone, Giulia Regazzo, Manuela Spagnuolo, Tonino Alonzi, Fabrizio Carlomosti, Maria Lucia Dell’Anna, Giulia Dell’Omo, Mauro Picardo, Paolo Ciana, Maurizio C. Capogrossi, Marco Tripodi, Alessandra Magenta, Maria Giulia Rizzo, Aymone Gurtner and Giulia Piaggio _

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Oncotarget. 2017; 8:2628-2646. https://doi.org/10.18632/oncotarget.12914

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Abstract

Lucia Cicchillitti1,*, Isabella Manni1,*, Carmine Mancone2,3, Giulia Regazzo4, Manuela Spagnuolo4, Tonino Alonzi2, Fabrizio Carlomosti5,, Maria Lucia Dell’Anna6, Giulia Dell’Omo7, Mauro Picardo6, Paolo Ciana8, Maurizio C. Capogrossi5, Marco Tripodi2,3, Alessandra Magenta5, Maria Giulia Rizzo4, Aymone Gurtner1,#, Giulia Piaggio1,#

1Department of Research, Advanced Diagnostics and Technological Innovation, SAFU Unit, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy

2National Institute for Infectious Diseases L. Spallanzani, IRCCS, Department of Epidemiology and Preclinical Research, 00149 Rome, Italy

3Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy

4Department of Research, Advanced Diagnostics and Technological Innovation, Genomic and Epigenetic Unit, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy

5Fondazione Luigi Maria Monti, Istituto Dermopatico dell’Immacolata-IRCCS, Laboratorio di Patologia Vascolare, 00167 Rome, Italy

6Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, 00144 Rome, Italy

7Department of Oncology and Hemato-Oncology and Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy

8Center 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 29th 2015

Correspondence to:

Giulia Piaggio, email: [email protected]

Aymone Gurtner, email: [email protected]

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.


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