Regulation of E2F1 activity by acetylation
Regulation of E2F1 activity by acetylation
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DOI：
10.1093/emboj/19.4.662
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发表时间：
2000-02-15
期刊：
影响因子：
11.4
通讯作者：
Kouzarides, T
中科院分区：
文献类型：
--
作者：
Martínez-Balbás, MA;Bauer, UM;Kouzarides, T
在细胞周期的G(1)期，E2F-RB复合物通过募集组蛋白去乙酰化酶活性来抑制转录。RE在G(1)/S边界的磷酸化会产生一池“自由”的E2F，刺激S期基因的转录。鉴于E2F1活性受p300/CBP乙酰化酶刺激，并被re相关的去乙酰化酶抑制，我们想知道E2F1是否受到乙酰化修饰的影响。我们发现p300/CBP相关因子P/CAF，以及在较小程度上p300/CBP本身，可以在体外乙酰化E2F1，并且细胞内E2F1被乙酰化。乙酰化位点位于E2F1 dna结合域附近，涉及E2F1、2和3高度保守的赖氨酸残基。P/CAF乙酰化对E2F1活性有三个功能影响：增加dna结合能力、激活电位和蛋白质半衰期。这些结果表明，乙酰化刺激了非re结合“自由”形式的E2F1的功能。与此一致，我们发现re相关的组蛋白去乙酰化酶可以使E2F1去乙酰化。这些结果表明乙酰化是一种新的调控修饰，可以刺激E2F1的激活功能。
During the G(1) phase of the cell cycle, an E2F-RB complex represses transcription, via the recruitment of histone deacetylase activity. Phosphorylation of RE at the G(1)/S boundary generates a pool of 'free' E2F, which theta stimulates transcription of S-phase genes. Given that E2F1 activity is stimulated by p300/CBP acetylase and repressed by an RE-associated deacetylase, we asked if E2F1 was subject to modification by acetylation. We show that the p300/CBP-associated factor P/CAF, and to a lesser extent p300/CBP itself, can acetylate E2F1 in vitro and that intracellular E2F1 is acetylated. The acetylation sites lie adjacent to the E2F1 DNA-binding domain and involve lysine residues highly conserved in E2F1, 2 and 3. Acetylation by P/CAF has three functional consequences on E2F1 activity: increased DNA-binding ability, activation potential and protein half-life. These results suggest that acetylation stimulates the functions of the non-RE bound 'free' form of E2F1. Consistent with this, we find that the RE-associated histone deacetylase can deacetylate E2F1. These results identify acetylation as a novel regulatory modification that stimulates E2F1's activation functions.