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Mol Biol Cell. 2008 Dec;19(12):5203-13. doi: 10.1091/mbc.E08-03-0295. Epub 2008 Sep 24.

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

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  • 1Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, 00158 Rome, Italy.

Abstract

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.

PMID:
18815279
PMCID:
PMC2592644
DOI:
10.1091/mbc.E08-03-0295
[PubMed - indexed for MEDLINE]
Free PMC Article
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