Data di Pubblicazione:
2019
Citazione:
The phosphorylatable Ser320 of NF-YA is involved in DNA binding of the NF-Y trimer / A. Bernardini, M. Lorenzo, M. Nardini, R. Mantovani, N. Gnesutta. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 33:4(2019), pp. 4790-4801. [10.1096/fj.201801989R]
Abstract:
Nuclear factor Y (NF-Y) is a transcription factor trimer binding to the functionally important CCAAT box, present in promoters of growth-promoting and cell cycle-regulated genes. The regulatory nuclear factor YA (NF-YA) subunit confers sequence-specificity to the histone-like nuclear factor YB/YC dimer. NF-YA harbors 2 serines-Ser320 and Ser326-shown to be phosphorylated by cyclin-dependent kinase 2. High-throughput proteomics data indicate that they are phosphorylated in vivo. Specifically, Ser320 makes structural contacts with the DNA phosphate backbone; Ser320-P is the major NF-YA phosphorylation isoform following overexpression in HeLa cells, increasing upon mitotic arrest. EMSA with recombinant Ala and Glu mutants confirm a role of Ser320, but not Ser326, in stabilization of DNA binding. Transactivation assays of the CCAAT-dependent MDR1 and RHOB promoters show loss in transcription function for Ser320Glu and Ser320Ala NF-YA mutants. Phylogenetic analysis of NF-YA proteins indicates that Ser320 is indeed evolutionarily conserved. We conclude that phosphorylation of this residue belongs to the core mechanisms of DNA-binding control, possibly driven by the necessity to unfasten binding of or to evict NF-Y from CCAAT sites under specific conditions of growth regulation.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
transcription factor; DNA-protein interactions; post-translational modification; cyclin-dependent kinase; histone-fold domain
Elenco autori:
A. Bernardini, M. Lorenzo, M. Nardini, R. Mantovani, N. Gnesutta
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