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

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.

Prognostic role of NF-YA splicing isoforms and Lamin A status in low grade endometrial cancer

“…Very interestingly, we observed an inverse correlation between NF-YAs and lamin A expression, thus further supporting the hypothesis of a possible involvement of NF-YAs in tumor differentiation and aggressiveness. In agreement with this, we have recently characterized a role for lamin A in counteracting NF-Y transcriptional activity in cancer cells [36]. Thus, we hypothesizes that concomitant expression of NF-YAs and lamin A down-modulation may be associated with an increased proliferation rate and a more invasive phenotype of cancer cells.…”

synder: inferring genomic orthologs from synteny maps

“…The canonical NF-Y is a heterotrimeric, eukaryotic transcription factor that is comprised of subunits NF-YA, NF-YB and NF-YC [31]. NF-Y has been associated with characteristics as diverse as cell division [32], cancer [33,34], drought tolerance [35], broad spectrum disease resistance [36], and carbon and nitrogen partitioning [37]. In animals and fungi, a single gene encodes each of the three NF-Y subunits.…”

SSEA3 and Sialyl Lewis a Glycan Expression Is Controlled by B3GALT5 LTR through Lamin A-NFYA and SIRT1-STAT3 Signaling in Human ES Cells

“…These findings suggest that the stem-cell markers SSEA3, sialyl Lewis a, and lamin A are not mediators of differentiation. Lamin A interacts with NFYA to block NFYA activity [44]. Lamin A reduces NFYA expression when it binds to the NFY complex at the CCAAT box on the NFYA promoter [43].…”

“…Activation by NFYAs or repression by NFYAl was diminished after deletion of the NFY-binding site on the B3GALT5-LTR promoter ( Figure 5D). The amount of NFYA and its activity is decreased by lamin A [43,44], and lamin A is an ES cell differentiation marker [45]. Lamin A was downregulated by RA treatment of NCCIT and H1 Oct4-EGFP cells ( Figure S5A).…”