Posttranslational Regulation of NF-YA Modulates NF-Y Transcriptional Activity

被引:45
作者
Manni, Isabella [1 ]
Caretti, Giuseppina [3 ]
Artuso, Simona [1 ]
Gurtner, Aymone [1 ]
Emiliozzi, Velia [1 ]
Sacchi, Ada [1 ]
Mantovani, Roberto [3 ]
Piaggio, Giulia [1 ,2 ]
机构
[1] Regina Elena Inst Canc Res, Mol Oncogenesis Lab, I-00158 Rome, Italy
[2] Regina Elena Inst Canc Res, Rome Oncogen Ctr, Dept Expt Oncol, I-00158 Rome, Italy
[3] Univ Milan, Biomol & Biotechnol Sci Dept, I-20133 Milan, Italy
关键词
D O I
10.1091/mbc.E08-03-0295
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:5203 / 5213
页数:11
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