Dephosphorylation of TORC initiates expression of the StAR gene
Dephosphorylation of TORC initiates expression of the StAR gene
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DOI：
10.1016/j.mce.2006.12.020
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发表时间：
2007-02
影响因子：
4.1
通讯作者：
H. Takemori;Mariko Kanematsu;Junko Kajimura;O. Hatano;Y. Katoh;Xing-zi Lin;L. Min;T. Yamazaki;J. Doi;M. Okamoto
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文献类型：
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作者：
H. Takemori;Mariko Kanematsu;Junko Kajimura;O. Hatano;Y. Katoh;Xing-zi Lin;L. Min;T. Yamazaki;J. Doi;M. Okamoto
已知的环状AMP反应元件(CRE)结合蛋白(CREB)在其Ser133被磷酸化时能够激活转录。然而，调节CREB活性的转导蛋白(TORC)是一种CREB特异性共激活剂，它以一种不依赖于磷酸丝氨酸133的方式上调CREB活性。有趣的是，TORC也受到磷酸化的调节；磷酸化形式是不活跃的，去磷酸化形式是活跃的。当PKA磷酸化CREB时，它同时抑制TORC激酶，并加速TORC的去磷酸化。在这篇报道中，我们发现一种酶抑制剂星形孢子素可以诱导Y1肾上腺皮质细胞中STAR基因的表达，这可能是由于脱磷转运蛋白的数量增加所致。已知STAR基因的表达受SF-1和CREB的调节，共激活子CBP/p300可能介导这两个因子的作用。我们使用KG501的实验也支持TORC在调控STAR基因表达中的重要性。KG501是磷酸化CREB和CBP/p300之间相互作用的破坏者。
Cyclic AMP responsive element (CRE) binding protein (CREB) is known to activate transcription when its Ser133 is phosphorylated. However, transducer of regulated CREB activity (TORC), a CREB specific co-activator, upregulates CREB activity in a phospho-Ser133-independent manner. Interestingly, TORC is also regulated by phosphorylation; the phospho-form is inactive, and the dephospho-form active. When PKA phosphorylates CREB, it inhibits TORC kinases simultaneously and accelerates dephosphorylation of TORC. We show in this report that staurosporine, a kinase inhibitor, induces the expression of the StAR gene in Y1 adrenocortical cells, possibly a result of an increase in the population of dephospho-TORC. The expression of the StAR gene is known to be regulated by SF-1 and CREB, and the co-activators CBP/p300 may mediate the actions of both factors. Our experiments using KG501, a disruptor of the interaction between phospho-CREB and CBP/p300, also support the importance of TORC in the regulation of StAR gene expression.