TY - JOUR
T1 - The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation
AU - Cicchillitti, Lucia
AU - Manni, Isabella
AU - Mancone, Carmine
AU - Regazzo, Giulia
AU - Spagnuolo, Manuela
AU - Alonzi, Tonino
AU - Carlomosti, Fabrizio
AU - Dell'Anna, Maria Lucia
AU - Dell'Omo, Giulia
AU - Picardo, Mauro
AU - Ciana, Paolo
AU - Capogrossi, Maurizio C
AU - Tripodi, Marco
AU - Magenta, Alessandra
AU - Rizzo, Maria Giulia
AU - Gurtner, Aymone
AU - Piaggio, Giulia
PY - 2017/1/10
Y1 - 2017/1/10
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.18632/oncotarget.12914
DO - 10.18632/oncotarget.12914
M3 - Article
C2 - 27793050
VL - 8
SP - 2628
EP - 2646
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 2
ER -