TOX3 regulates calcium-dependent transcription in neurons

TOX3 regulates calcium-dependent transcription in neurons
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DOI:
10.1073/pnas.0805555106
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发表时间:
2009-02-24
影响因子:
11.1
通讯作者:
Ghosh, Anirvan
Ghosh, Anirvan
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yuan, Shauna H.;Qiu, Zilong;Ghosh, Anirvan

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我们报告的TOX 3,参与介导钙依赖性转录的高迁移率族蛋白的克隆和表征。使用反式激活因子捕获筛选将TOX 3鉴定为钙依赖性反式激活因子。我们发现,TOX 3与cAMP反应元件(CRE)结合蛋白(CREB)和CREB结合蛋白(CBP)相互作用,通过RNAi敲低内源性TOX 3导致钙诱导的c-fos表达显著降低,并完全抑制c-fos启动子的钙激活。TOX 3对钙依赖性转录的影响需要CRE元件。这些观察结果表明TOX 3是钙依赖性转录的重要调节因子,并表明TOX 3通过与CREB-CBP复合物的结合对CREB介导的转录发挥作用。
We report the cloning and characterization of TOX3, a high mobility group box protein involved in mediating calcium-dependent transcription. TOX3 was identified as a calcium-dependent transactivator using the Transactivator Trap screen. We find that TOX3 interacts with both cAMP response element (CRE)-binding protein (CREB) and CREB-binding protein (CBP), and knockdown of the endogenous TOX3 by RNAi leads to significant reduction of calcium-induced c-fos expression and complete inhibition of calcium activation of the c-fos promoter. The effects of TOX3 on calcium-dependent transcription require the CRE elements. These observations identify TOX3 as an important regulator of calcium-dependent transcription and suggest that TOX3 exerts its effect on CRE-mediated transcription via its association with the CREB-CBP complex.