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, Giulia Piaggio

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2628-2646
Number of pages19
JournalOncotarget
Volume8
Issue number2
DOIs
Publication statusE-pub ahead of print - Oct 26 2016

Keywords

  • Cell cycle
  • Euchromatin
  • Nuclear lamina
  • Proliferation
  • Transcription

ASJC Scopus subject areas

  • Oncology

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