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首页> 外文期刊>Molecular and Cellular Biology >Simian virus 40 small tumor antigen inhibits dephosphorylation of protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation.
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Simian virus 40 small tumor antigen inhibits dephosphorylation of protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation.

机译：猿猴病毒40小肿瘤抗原抑制蛋白激酶A磷酸化的CREB的去磷酸化，并调节CREB的转录刺激。

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We report that the small tumor (small-t) antigen of simian virus 40 (SV40) forms complexes with nuclear protein phosphatase 2A (PP2A) and regulates the phosphorylation and transcriptional transactivation function of the cyclic AMP (cAMP)-regulatory element binding protein (CREB). PP2A coimmunoprecipitated with small t from nuclear extracts from HepG2 cells expressing small t or from rat liver nuclear extracts to which recombinant small t was added. Protein phosphatase 1 was not detected in small-t immunoprecipitates. In HepG2 cells expressing small t, dibutyryl-cAMP (Bt2cAMP) stimulated the phosphorylation of CREB 65-fold, whereas CREB phosphorylation was stimulated only 5- to 8-fold by Bt2cAMP in cells not expressing small t. Small t also inhibited the dephosphorylation of cAMP-dependent protein kinase (PKA)-phosphorylated CREB in rat liver nuclear extracts. In cells expressing small t, Bt2cAMP-stimulated transcription from the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter was enhanced over the level of transcription from the PEPCK promoter in cells not expressing small t. Small t also enhanced Bt2cAMP-stimulated transcription from a Gal4-responsive promoter in cells expressing a chimeric protein containing the Gal4 DNA-binding domain linked to the CREB transactivation domain. However, small t did not stimulate transcription either from a 5' deletion mutant of the PEPCK promoter that is not able to bind CREB or from the Gal4-responsive promoter in the absence of the Gal4-CREB protein. These data suggest that small t enhances Bt2cAMP-stimulated gene transcription by inhibiting the dephosphorylation of PKA-phosphorylated CREB by nuclear PP2A. These findings support previous observations that nuclear PP2A is the primary phosphatase that dephosphorylates PKA-phosphorylated CREB.
机译：我们报道猿猴病毒40（SV40）的小肿瘤（small-t）抗原与核蛋白磷酸酶2A（PP2A）形成复合物并调节环AMP（cAMP）调控元件结合蛋白的磷酸化和转录反式激活功能（ CREB）。从表达小t的HepG2细胞的核提取物中或从添加了重组小t的大鼠肝核提取物中用小t共沉淀PP2A。在小t免疫沉淀物中未检测到蛋白磷酸酶1。在表达小t的HepG2细胞中，二丁酰cAMP（Bt2cAMP）刺激CREB磷酸化65倍，而在不表达小t的细胞中，Bt2cAMP仅刺激CREB磷酸化5至8倍。 Small t还抑制大鼠肝核提取物中cAMP依赖性蛋白激酶（PKA）磷酸化的CREB的去磷酸化。在表达小t的细胞中，Bt2cAMP刺激的磷酸烯醇丙酮酸羧激酶（PEPCK）基因启动子的转录比不表达小t的细胞中PEPCK启动子的转录水平更高。在表达嵌合蛋白的细胞中，Small t还增强了来自Gal4响应启动子的Bt2cAMP刺激的转录，该嵌合蛋白包含与CREB反式激活结构域连接的Gal4 DNA结合结构域。然而，小t既不能刺激不能结合CREB的PEPCK启动子的5'缺失突变体的刺激，也不能刺激缺少Gal4-CREB蛋白的Gal4反应性启动子的转录。这些数据表明，小t通过抑制核PP2A对PKA磷酸化的CREB的去磷酸化作用来增强Bt2cAMP刺激的基因转录。这些发现支持以前的观察，即核PP2A是使PKA磷酸化的CREB脱磷酸的主要磷酸酶。

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