期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 16, 期 4, 页码 412-420出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1583
关键词
-
资金
- FIRB program of the Ministero dell'Istruzione, Universita e Ricerca,'' Italy
- Fondazione CRTrieste'' of Trieste, Italy
In eukaryotic cells, the cell-division cycle (CDC)-6 protein is essential to promote the assembly of pre-replicative complexes in the early G1 phase of the cell cycle, a process requiring tight regulation to ensure that proper origin licensing occurs once per cell cycle. Here we show that, in late G1 and early S phase, CDC6 is found in a complex also containing Cyclin A, cyclin-dependent kinase (CDK)-2 and the acetyltransferase general control nonderepressible 5 (GCN5). GCN5 specifically acetylates CDC6 at three lysine residues flanking its cyclin-docking motif, and this modification is crucial for the subsequent phosphorylation of the protein by Cyclin A-CDKs at a specific residue close to the acetylation site. GCN5-mediated acetylation and site-specific phosphorylation of CDC6 are both necessary for the relocalization of the protein to the cell cytoplasm in the S phase, as well as to regulate its stability. This two-step, intramolecular regulatory program by sequential modification of CDC6 seems to be essential for proper S-phase progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据