Effects of B-Myb on gene transcription - Phosphorylation-dependent activity and acetylation by p300
Effects of B-Myb on gene transcription - Phosphorylation-dependent activity and acetylation by p300
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DOI：
10.1074/jbc.m105112200
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发表时间：
2002-02-08
影响因子：
4.8
通讯作者：
Rizzino, A
中科院分区：
文献类型：
--
作者：
Johnson, LR;Johnson, TK;Rizzino, A
转录因子B-Myb是一种细胞周期调节磷蛋白，通过许多基因的转录调节参与细胞周期进程。在这项研究中，我们表明，成纤维细胞生长因子-4（FGF-4）基因的启动子在HeLa细胞中被B-Myb强烈激活，它可以作为一种新的诊断工具，用于评估B-Myb活性。具体地，检查B-Myb缺失突变体，并鉴定FGF-4启动子活化所需的B-Myb结构域。使用磷酸化缺陷的突变形式的B-Myb，我们还表明，磷酸化是必不可少的B-Myb的活动。此外，缺乏所有鉴定的磷酸化位点并且几乎没有活性的B-Myb的突变形式可以作为显性阴性发挥作用并且抑制野生型B-Myb活性。乙酰化是另一种已知影响其他Myb家族成员活性的翻译后修饰。我们表明，B-Myb是乙酰化的辅激活蛋白p300。我们还表明，溴和组蛋白乙酰转移酶结构域的p300是足够的相互作用和乙酰化B-Myb。这些数据表明B-Myb的磷酸化是活性的必要修饰，并且B-Myb的乙酰化可能在B-Myb活性中起作用。
The transcription factor B-Myb is a cell-cycle regulated phosphoprotein involved in cell cycle progression through the transcriptional regulation of many genes. In this study, we show that the promoter of the fibroblast growth factor-4 (FGF-4) gene is strongly activated by B-Myb in HeLa cells and it can serve as a novel diagnostic tool for assessing B-Myb activity. Specifically, B-Myb deletion mutants were examined and domains of B-Myb required for activation of the FGF-4 promoter were identified. Using phosphorylation-deficient mutant forms of B-Myb, we also show that phosphorylation is essential for B-Myb activity. Moreover, a mutant form of B-Myb, which lacks all identified phosphorylation sites and which has little activity, can function as a dominant-negative and suppress wild-type B-Myb activity. Acetylation is another post-translational modification known to affect the activity of other Myb family members. We show that B-Myb is acetylated by the coactivator p300. We also show that the bromo and histone acetyltransferase domains of p300 are sufficient to interact with and acetylate B-Myb. These data indicate that phosphorylation of B-Myb is an essential modification for activity and that acetylation of B-Myb may play a role in B-Myb activity.