Posttranslational regulation of NF-YA modulates NF-Y transcriptional activity.

NF-Y binds to CCAAT motifs in the promoter region of a variety of genes involved in cell cycle progression. The NF-Y complex comprises three subunits, NF-YA, -YB, and -YC, all required for DNA binding. Expression of NF-YA fluctuates during the cell cycle and is down-regulated in postmitotic cells, indicating its ...
role as the regulatory subunit of the complex. Control of NF-YA accumulation is posttranscriptional, NF-YA mRNA being relatively constant. Here we show that the levels of NF-YA protein are regulated posttranslationally by ubiquitylation and acetylation. A NF-YA protein carrying four mutated lysines in the C-terminal domain is more stable than the wild-type form, indicating that these lysines are ubiquitylated Two of the lysines are acetylated in vitro by p300, suggesting a competition between ubiquitylation and acetylation of overlapping residues. Interestingly, overexpression of a degradation-resistant NF-YA protein leads to sustained expression of mitotic cyclin complexes and increased cell proliferation, indicating that a tight regulation of NF-YA levels contributes to regulate NF-Y activity.
Mesh Terms:
Amino Acid Sequence, Animals, CCAAT-Binding Factor, Cell Line, Gene Expression Regulation, Humans, Lysine, Mice, Molecular Sequence Data, Promoter Regions, Genetic, Proteasome Endopeptidase Complex, Protein Processing, Post-Translational, Protein Subunits, Recombinant Fusion Proteins, Sequence Alignment, Transcription, Genetic, Ubiquitination, p300-CBP Transcription Factors
Mol. Biol. Cell
Date: Dec. 01, 2008
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