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

Isabella Manni, Giuseppina Caretti, Simona Artuso, Aymone Gurtner, Velia Emiliozzi, Ada Sacchi, Roberto Mantovani, Giulia Piaggio

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5203-5213
Number of pages11
JournalMolecular Biology of the Cell
Volume19
Issue number12
DOIs
Publication statusPublished - Dec 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Posttranslational regulation of NF-YA modulates NF-Y transcriptional activity'. Together they form a unique fingerprint.

Cite this