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.
Manni
Isabella
I
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, 00158 Rome, Italy.
Caretti
Giuseppina
G
Artuso
Simona
S
Gurtner
Aymone
A
Emiliozzi
Velia
V
Sacchi
Ada
A
Mantovani
Roberto
R
Piaggio
Giulia
G
D000595:Amino Acid Sequence; D000818:Animals; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014158:Transcription, Genetic; D054875:Ubiquitination; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D023081:CCAAT-Binding Factor; D008239:Lysine; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C492060:Nfya protein, mouse