Transcription intermediary factor 1gamma decreases protein expression of the transcriptional cofactor, LIM-domain-binding 1.

Transcription intermediary factor 1gamma decreases protein expression of the transcriptional cofactor, LIM-domain-binding 1.
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DOI:
10.1016/j.bbrc.2010.04.160
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发表时间:
2010-06-04
影响因子:
3.1
通讯作者:
Maurer, Richard A.
Maurer, Richard A.
中科院分区:
生物学4区
文献类型:
--
作者:
Howard, Paul W.;Ransom, David G.;Maurer, Richard A.

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LIM结构域结合1(LDB 1)是参与调控复合物形成的辅因子,所述调控复合物涉及含有LIM结构域的转录因子以及其它因子。我们检测了转录中间因子1γ(TIF 1 γ)降低LDB 1表达的能力。发现TIF 1 γ的表达载体降低LDB 1的表达。发现破坏TIF 1 γ的泛素连接酶活性的突变阻断了TIF 1 γ降低LDB 1表达的能力。蛋白酶体抑制剂也能够阻断TIF 1 γ对LDB 1的作用。免疫沉淀研究提供了LDB 1在完整细胞中与TIF 1 γ相互作用的证据。斑马鱼胚胎中TIF 1 γ的敲低导致LDB 1表达增加,为TIF 1 γ在调节LDB 1表达中的生理作用提供了证据。报告基因分析表明,TIF 1 γ可以改变LIM-homeodomain转录因子应答启动子的活性。这些研究与TIF 1 γ作用于LDB 1泛素化导致LDB 1降解和LDB 1依赖性启动子转录变化的模型一致。
LIM-domain-binding 1 (LDB1) is a cofactor that participates in formation of regulatory complexes involving transcription factors containing LIM domains as well as other factors. We have examined the ability of transcriptional Intermediary factor 1γ (TIF1γ) to decrease LDB1 expression. An expression vector for TIF1γ was found to decrease expression of LDB1. A mutation which disrupts the ubiquitin ligase activity of TIF1γ was found to block the ability of TIF1γ to decrease LDB1 expression. Proteasome inhibitors were also able to block TIF1γ effects on LDB1. Immunoprecipitation studies provided evidence that LDB1 interacts with TIF1γ in intact cells. Knockdown of TIF1γ in zebrafish embryos led to increased expression of LDB1 providing evidence for a physiological role of TIF1γ in regulating LDB1 expression. Reporter gene assays demonstrated that TIF1γ can alter the activity of LIM-homeodomain transcription factor-responsive promoters. These studies are consistent with a model in which TIF1γ acts to ubiquitinate LDB1 leading to degradation of LDB1 and changes in transcription of LDB1-dependent promoters.
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