Chang Wen-Chang
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Prostaglandins Other Lipid Mediat. 2003 Jul;71(3-4):277-85. doi: 10.1016/s1098-8823(03)00048-0.
Human 12(S)-lipoxygenase is a platelet-type 12(S)-lipoxyenase. Its expression is detected in human erythroleukemia cells, human skin epidermal cells and human epidermoid carcinoma A431 cells. Treatment of A431 cells with EGF or PMA induces the gene expression of human 12(S)-lipoxygenase. The induction of gene expression is mediated through the cell signaling of MAPK activation, followed by the induction of c-Jun expression. The transcription factor Sp1 binding to the two Sp1 recognition motifs residing at -158 to 150 bp and -123 to 114 bp in the gene promoter is found to be essential for both EGF- and PMA-induced gene expression of human 12(S)-lipoxygenase. However, no change of Sp1 binding to GC-rich sequence was observed while no AP-1-binding site can be found in the responsive region of the promoter in EGF- and PMA-induced promoter activation of the human 12(S)-lipoxygenase gene. Since both of the transcription factors c-Jun and Sp1 are prerequisite for EGF and PMA response, interaction between c-Jun and Sp1 may account for the functional regulation of human 12(S)-lipoxygenase gene regulation. The direct and cooperative interaction between c-Jun and Sp1 induced by EGF or PMA activates the expression of the human 12(S)-lipoxygenase gene. Therefore, Sp1 may serve at least in part as a carrier to bring c-Jun to the promoter, thu's transactivating the transcriptional activity of the human 12(S)-lipoxygenase gene.
人12(S)-脂氧合酶是一种血小板型12(S)-脂氧合酶。在人红白血病细胞、人皮肤表皮细胞和人表皮样癌A431细胞中可检测到其表达。用表皮生长因子（EGF）或佛波酯（PMA）处理A431细胞可诱导人12(S)-脂氧合酶的基因表达。基因表达的诱导是通过丝裂原活化蛋白激酶（MAPK）激活的细胞信号传导介导的，随后诱导c-Jun表达。发现转录因子Sp1与位于基因启动子中-158至-150 bp和-123至-114 bp处的两个Sp1识别基序结合，对于EGF和PMA诱导的人12(S)-脂氧合酶基因表达至关重要。然而，在EGF和PMA诱导的人12(S)-脂氧合酶基因启动子激活过程中，未观察到Sp1与富含GC序列的结合发生变化，且在启动子的反应区域未发现AP-1结合位点。由于转录因子c-Jun和Sp1都是EGF和PMA反应的先决条件，c-Jun和Sp1之间的相互作用可能解释了人12(S)-脂氧合酶基因调控的功能调节。EGF或PMA诱导的c-Jun和Sp1之间的直接协同相互作用激活了人12(S)-脂氧合酶基因的表达。因此，Sp1可能至少部分作为一种载体，将c-Jun带到启动子，从而反式激活人12(S)-脂氧合酶基因的转录活性。
