An apparent autocrine mechanism amplifies the dexamethasone- and retinoic acid-induced expression of mouse lipocalin-encoding gene 24p3
An apparent autocrine mechanism amplifies the dexamethasone- and retinoic acid-induced expression of mouse lipocalin-encoding gene 24p3
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DOI：
10.1016/0378-1119(95)00896-9
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发表时间：
1996-05-08
期刊：
影响因子：
3.5
通讯作者：
Kress, M
中科院分区：
文献类型：
--
作者：
GarayRojas, E;Harper, M;Kress, M
我们对小鼠24p3基因进行了分离、测序和表征。24p3蛋白是脂钙蛋白家族的一员，由疏水配体的分泌转运体组成。24p3 cDNA最初是在寻找sv40诱导的有丝分裂反应中过表达的基因时分离出来的[Hraba-Renevey等人，Oncogene 4(1989) 601-608]。24p3由6个外显子、活内含子和793 bp的5'调控区组成。通过引物延伸鉴定转录起始点（tsp）。假设的调控元件，包括一个塔塔样盒子和两个糖皮质激素响应核心元件（GRE），已经在s侧区域被定位。基于这一观察结果，我们检测了糖皮质激素（地塞米松，Dex）对24p3表达的影响。Dex在没有新生蛋白合成的情况下显著诱导24p3的表达。这种激活被一种明显的自分泌机制进一步放大。维甲酸也得到了类似的结果。利用猫报告基因系统，我们已经证明24p3的5'-侧翼区域具有Dex诱导性。此外，我们已经确定了24p3启动子的43-bp区域，这是Dex响应性所需的。根据这些结果讨论了生物学意义。
We have isolated, sequenced and characterized the mouse 24p3 gene. The 24p3 protein is a member of the lipocalin family comprising secreted transporters of hydrophobic ligands. The 24p3 cDNA had been initially isolated during a search for genes overexpressed during a SV40-induced mitotic reaction [Hraba-Renevey et al., Oncogene 4 (1989) 601-608]. 24p3 comprises six exons, live introns and 793 bp of 5' regulatory region. The transcription start point (tsp) was identified by primer extension. Putative regulatory elements, including a TATA-like box and two glucocorticoid responsive core elements (GRE), have been mapped in the S-flanking region. Based on this observation, we examined the effect of a glucocorticoid (dexamethasone, Dex) on 24p3 expression. Dex induced the expression of 24p3 dramatically in the absence of de novo protein synthesis. This activation was further amplified by an apparent autocrine mechanism. Similar results were obtained with retinoic acid. Using the cat reporter gene system, we have shown that the 5'-flanking region of 24p3 confers Dex inducibility. Furthermore, we have identified a 43-bp region of the 24p3 promoter required for the Dex responsiveness. The biological implications are discussed in light of these results.