Sp100 interacts with ETS-1 and stimulates its transcriptional activity

Sp100 interacts with ETS-1 and stimulates its transcriptional activity
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DOI:
10.1128/mcb.22.8.2687-2702.2002
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发表时间:
2002-04-01
影响因子:
5.3
通讯作者:
Wasylyk, B
Wasylyk, B
中科院分区:
生物学2区
文献类型:
--
作者:
Wasylyk, C;Schlumberger, SE;Wasylyk, B

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细胞核被高度组织成空间上分离生理过程的不同域。其中一个结构域,Sp100-早幼粒细胞白血病蛋白核体(NB),涉及病理过程,如癌症和病毒感染,但其功能仍然知之甚少。我们发现Sp100在物理和功能上与ETS-1相互作用,并且NB形态受到ETS-1的影响。ETS-1是转录因子ets家族的一员,是生理和病理过程的关键介质。我们发现Sp100与ETS-1的两个区域(结构域A+B和D+E+F)相互作用。ETS-1改变NB,同时保持整个核定位,显然是通过募集核心成分Sp100远离NB。Sp100通过除了相互作用结构域之外还涉及ETS-1的激活(C)结构域的机制,强烈增加天然和ETS-聚焦启动子的ETS-1激活。Sp100作为一种新的辅激活因子,增强ETS-1的激活功能。我们的研究结果提供了一个重要的新的核结构和基因表达的重要调节器之间的连接。
The cell nucleus is highly organized into distinct domains that spatially separate physiological processes. One of these domains, the Sp100-promyelocytic leukemia protein nuclear body (NB), is implicated in pathological processes, such as cancer and viral infection, yet its functions remain poorly understood. We show here that Sp100 interacts physically and functionally with ETS-1 and that NB morphology is affected by ETS-1. ETS-1 is a member of the ets family of transcription factors, which are key mediators of physiological and pathological processes. We have found that Sp100 interacts with two regions of ETS-1 (domains A+B and D+E+F). ETS-1 alters NBs while remaining localized throughout the nucleus, apparently by recruitment of the core component Sp100 away from the NBs. Sp100 strongly increases ETS-1 activation of natural and ets-focused promoters, through a mechanism involving the activation (C) domain of ETS-1 in addition to the interaction domains. Sp100 acts as a novel coactivator that potentiates the activator function of ETS-1. Our results provide an important new connection between nuclear structures and an important regulator of gene expression.