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.
The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation / L. Cicchillitti, I. Manni, C. Mancone, G. Regazzo, M. Spagnuolo, T. Alonzi, F. Carlomosti, M.L. Dell'Anna, G. Dell'Omo, M. Picardo, P. Ciana, M.C. Capogrossi, M. Tripodi, A. Magenta, M.G. Rizzo, A. Gurtner, G. Piaggio. - In: ONCOTARGET. - ISSN 1949-2553. - 8:2(2017 Jan 10), pp. 2628-2646.
|Titolo:||The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation|
|Parole Chiave:||cell cycle; euchromatin; nuclear lamina; proliferation; transcription|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||10-gen-2017|
|Data ahead of print / Data di stampa:||26-ott-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.18632/oncotarget.12914|
|Appare nelle tipologie:||01 - Articolo su periodico|