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首页> 外文期刊>Molecular and Cellular Biology >Loss of serum response element-binding activity and hyperphosphorylation of serum response factor during cellular aging.
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Loss of serum response element-binding activity and hyperphosphorylation of serum response factor during cellular aging.

机译：细胞衰老过程中血清反应因子结合活性的丧失和血清反应因子的过度磷酸化。

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Human diploid fibroblasts undergo a limited number of population doublings in vitro and are used widely as a model of cellular aging. Despite growing evidence that cellular aging occurs as a consequence of altered gene expression, little is known about the activity of transcription factors in aging cells. Here, we report a dramatic reduction in the ability of proteins extracted from the nuclei of near-senescent fibroblasts to bind the serum response element which is necessary for serum-induced transcription of the c-fos gene. In contrast, the activities of proteins binding to the RNA polymerase core element, TATA, as well as to the cyclic AMP response element were maintained during cellular aging. While no major differences in the expression of the serum response factor (SRF) that binds the serum response element were seen between early-passage and late-passage cells, hyperphosphorylation of SRF was observed in near-senescent cells. Furthermore, removal of phosphatase inhibitors during the isolation of endogenous nuclear proteins restored the ability of SRF isolated from old cells to bind the SRE. These data, therefore, indicate that hyperphosphorylation of SRF plays a role in altering the ability of this protein to bind to DNA and regulate gene expression in senescent cells.
机译：人二倍体成纤维细胞在体外经历有限的群体倍增，并被广泛用作细胞衰老的模型。尽管越来越多的证据表明细胞衰老是由于基因表达改变而发生的，但对于衰老细胞中转录因子的活性知之甚少。在这里，我们报告从近衰老的成纤维细胞的核中提取的蛋白质结合血清反应元件的能力急剧下降，这是血清诱导的c-fos基因转录所必需的。相反，在细胞衰老过程中，蛋白质与RNA聚合酶核心元件TATA以及环状AMP反应元件结合的活性得以维持。虽然在早期传代细胞和晚期传代细胞之间未观察到与血清反应因子结合的血清反应因子（SRF）表达的主要差异，但在近衰老细胞中观察到SRF的过度磷酸化。此外，在内源性核蛋白分离过程中去除磷酸酶抑制剂可恢复从旧细胞分离的SRF结合SRE的能力。因此，这些数据表明SRF的过度磷酸化在改变该蛋白质结合DNA和调节衰老细胞中基因表达的能力中起作用。

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