Yang Shen-Hsi, Sharrocks Andrew D
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Biochem Soc Symp. 2006(73):121-9. doi: 10.1042/bss0730121.
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.
ETS 结构域转录因子 Elk-1 受丝裂原活化蛋白激酶（MAPK）信号通路激活后通过磷酸化作用进行调控。这种磷酸化作用引发了一系列分子事件，使 Elk-1 从转录沉默状态转变为高活性状态，随后又回到基础水平。同时，细胞外信号调节激酶（ERK）MAPK 信号通路的激活导致 Elk-1 失去小泛素相关修饰物（SUMO）的修饰。由于 SUMO 赋予 Elk-1 抑制特性，ERK 介导的 SUMO 缺失在 ERK 信号通路促进 Elk-1 激活的同时导致去抑制。因此，采用了一种两步机制将 Elk-1 转变为其完全激活状态。在此，将讨论 Elk-1 状态发生这些变化的潜在分子事件，以及 PIASxα[信号转导子和转录激活子（STAT）xα 的蛋白抑制剂]作为促进这一过程的共激活因子的作用。
