The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb
The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb
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DOI：
10.1101/gad.10.15.1858
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发表时间：
1996-08-01
影响因子：
10.5
通讯作者：
Ness, SA
中科院分区：
文献类型：
--
作者：
Dash, AB;Orrico, FC;Ness, SA
c-Myb转录因子是一种原癌蛋白，其潜在的转化活性可以通过截短任一末端来揭示。由于Myb的两端都参与负调控，我们测试了它们是否可以在双杂交试验中结合，并确定了一个羧基末端基序，与氨基末端DNA结合结构域相互作用。ET; ES基序在脊椎动物c-Myb蛋白中是高度保守的，并且包含先前参与c-Myb负调控的已知磷酸化位点。有趣的是，相关的EVES基序存在于p100中，p100是一种在不同物种中发现的普遍表达的转录共激活因子。我们表明p100与c-Myb相互作用并影响c-Myb的活性，暗示它参与c-Myb的调节、分化和细胞生长。我们的研究结果表明，Myb是由一种新的机制，其中分子内的相互作用和构象变化控制的Myb，p100，和转录装置之间的分子间协会。
The c-Myb transcription factor is a proto-oncoprotein whose latent transforming activity can be unmasked by truncation of either terminus. Because both ends of Myb are involved in negative regulation, we tested whether they could associate in a two-hybrid assay and identified a carboxy-terminal motif that interacts with the amino-terminal DNA-binding domain. The ET;ES motif is highly conserved in vertebrate c-Myb proteins and contains a known site of phosphorylation previously implicated in the negative regulation of c-Myb. Interestingly, a related EVES motif is present in p100, a ubiquitously expressed transcriptional coactivator found in diverse species, We show that p100 interacts with and influences the activity of c-Myb, implicating it in the regulation of c-Myb, differentiation, and cell growth. Our results suggest that Myb is regulated by a novel mechanism in which intramolecular interactions and conformational changes control the intermolecular associations among Myb, p100, and the transcriptional apparatus.