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STAMP a Novel Predicted Factor Assisting TIF2 Actions in Glucocorticoid Receptor-Mediated Induction and Repression

机译:STAMP一种在糖皮质激素受体介导的诱导和抑制中协助TIF2作用的新型预测因子

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摘要

The coactivator TIF2 was predicted to interact with an unknown factor to modify both the relative inhibition in glucocorticoid receptor (GR)-mediated gene repression and several parameters of agonists and antisteroids in GR-regulated induction. Here, we describe the isolation and characterization of the predicted factor as a new 1,277-amino-acid endogenous protein (STAMP). STAMP associates with coactivators (TIF2 and SRC-1) and is selective for a subset of the steroiduclear receptors including GRs. Transfected STAMP increases the effects of TIF2 in GR-mediated repression and induction. Conversely, the levels of both induction and repression of endogenous genes are reduced when STAMP small interfering RNAs are used to lower the level of endogenous STAMP. Endogenous STAMP colocalizes with GR in intact cells and is recruited to the promoters of endogenous GR-induced and -repressed genes. We suggest that STAMP is an important new, downstream component of GR action in both gene activation and gene repression.
机译:预计共激活因子TIF2与未知因子相互作用,以修饰糖皮质激素受体(GR)介导的基因阻遏的相对抑制以及GR调节诱导中激动剂和抗类固醇的几个参数。在这里,我们描述了预测因子的分离和表征,它是一种新的1,277个氨基酸的内源蛋白(STAMP)。 STAMP与辅助激活剂(TIF2和SRC-1)结合,对部分类固醇/核受体(包括GRs)具有选择性。转染的STAMP增加了TIF2在GR介导的阻遏和诱导中的作用。相反,当使用STAMP小干扰RNA降低内源STAMP的水平时,内源基因的诱导和抑制水平都会降低。内源性STAMP与GR在完整细胞中共定位,并被募集到内源性GR诱导和抑制的基因的启动子。我们建议,STAMP是基因激活和基因阻抑中GR行动的重要的新的下游组成部分。

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