Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1.
Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1.
复制标题
DOI：
10.1042/bss0730121
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Shen-hsi Yang;A. Sharrocks
中科院分区：
文献类型：
--
作者：
Shen-hsi Yang;A. Sharrocks
ETS-结构域转录因子Elk-1通过响应MAPK（促分裂原活化蛋白激酶）途径的活化的磷酸化来调节。这种磷酸化引发了一系列分子事件，将Elk-1从转录沉默状态转化为高度活跃状态，然后回到基础水平。同时，ERK（细胞外信号调节激酶）MAPK通路的激活导致SUMO（小泛素相关修饰剂）对Elk-1的修饰丧失。由于SUMO赋予Elk-1抑制特性，ERK介导的SUMO缺失导致去抑制，同时ERK途径促进Elk-1的活化。因此，采用两步机制将Elk-1转化为其完全活化状态。在这里，这些变化背后的Elk-1状态的分子事件，和PIASxalpha [激活STAT（信号转导和转录激活因子）xalpha的蛋白质抑制剂]作为促进这一过程的共激活剂的作用，进行了讨论。
The ETS-domain transcription factor Elk-1 is regulated by phosphorylation in response to activation of the MAPK (mitogen-activated protein kinase) pathways. This phosphorylation triggers a series of molecular events that convert Elk-1 from a transcriptionally silent state into a highly active state and then back to a basal level. At the same time, activation of the ERK (extracellular-signal-regulated kinase) MAPK pathway leads to loss of modification of Elk-1 by SUMO (small ubiquitin-related modifier). As SUMO imparts repressive properties on Elk-1, ERK-mediated SUMO loss leads to de-repression at the same time as the ERK pathway promotes activation of Elk-1. Thus a two-step mechanism is employed to convert Elk-1 into its fully activated state. Here, the molecular events underlying these changes in Elk-1 status, and the role of PIASxalpha [protein inhibitor of activated STAT (signal transducer and activator of transcription) xalpha] as a co-activator that facilitates this process, are discussed.