Overexpression of c-Fos is sufficient to stimulate tyrosine hydroxylase (TH) gene transcription in rat pheochromocytoma PC18 cells.
Overexpression of c-Fos is sufficient to stimulate tyrosine hydroxylase (TH) gene transcription in rat pheochromocytoma PC18 cells.
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c-Fos 的过度表达足以刺激大鼠嗜铬细胞瘤 PC18 细胞中的酪氨酸羟化酶 (TH) 基因转录。
DOI：
10.1046/j.0022-3042.2001.00692.x
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发表时间：
2002
影响因子：
4.7
通讯作者：
Tank,AWilliam
中科院分区：
文献类型：
--
作者：
Sun,Baoyong;Tank,AWilliam
酪氨酸羟化酶基因近端启动子内的 AP1 位点对于基因对多种刺激的反应至关重要。该基因的刺激通常与 AP1 转录因子 c-Fos 的诱导有关。然而，许多刺激会激活或诱导多个转录因子，这些转录因子与该 AP1 位点或基因近端启动子内的其他位点相互作用。因此，目前尚不清楚 c-Fos 诱导本身是否足以刺激酪氨酸羟化酶基因。在这项研究中，我们产生了大鼠嗜铬细胞瘤 PC18 细胞，这些细胞在 tet 诱导系统的控制下过表达 c-Fos。我们证明，c-Fos 的诱导会导致酪氨酸羟化酶基因转录率的显着刺激（使用核连续分析测定）。这种刺激在数量上与 c-Fos 的诱导密切相关，并且显然不需要 c-Fos 的磷酸化。该反应部分取决于酪氨酸羟化酶近端启动子内的 AP1 位点。然而，与内源基因相比，近端启动子对 c-Fos 诱导的反应相对较小。因此，我们的结果表明，c-Fos 通过依赖和独立于近端启动子 AP1 位点的多种机制对酪氨酸羟化酶基因发挥影响。
The AP1 site within the tyrosine hydroxylase gene proximal promoter is essential for the response of the gene to numerous stimuli. Stimulation of this gene is often associated with induction of the AP1 transcription factor, c‐Fos. However, many stimuli activate or induce multiple transcription factors that interact with this AP1 site or other sites within the gene's proximal promoter. Hence, it remains unclear whether c‐Fos induction by itself is sufficient to stimulate the tyrosine hydroxylase gene. In this study we produce rat pheochromocytoma PC18 cells that overexpress c‐Fos under control of the tet‐inducible system. We demonstrate that induction of c‐Fos leads to dramatic stimulation of tyrosine hydroxylase gene transcription rate measured using nuclear run‐on assays. This stimulation is closely associated quantitatively with the induction of c‐Fos and does not apparently require phosphorylation of c‐Fos. The response is partially dependent on the AP1 site within the tyrosine hydroxylase proximal promoter. However, the response of the proximal promoter to c‐Fos induction is relatively small compared with that of the endogenous gene. Consequently, our results suggest that c‐Fos exerts its influence on the tyrosine hydroxylase gene via multiple mechanisms that are dependent and independent of the proximal promoter AP1 site.