Interleukin-1 or phorbol induction of the stromelysin promoter requires an element that cooperates with AP-1.
Interleukin-1 or phorbol induction of the stromelysin promoter requires an element that cooperates with AP-1.
复制标题
Interleukin-1 或佛波醇对溶基质素启动子的诱导需要与 AP-1 协同作用的元件。
DOI：
10.1093/nar/19.2.335
复制
发表时间：
1991
影响因子：
14.9
通讯作者：
Brinckerhoff,CE
中科院分区：
文献类型：
--
作者：
Sirum-Connolly,K;Brinckerhoff,CE
Interieukin-1 是炎症介质或促进肿瘤的佛波酯，可诱导基质溶解素的转录，基质溶解素是一种金属蛋白酶，可降解细胞外基质分子，在类风湿性关节炎等疾病中过度表达。诱导人溶基质素启动子转录所需的序列包含在 46 个碱基对片段上。该片段包含与转录因子激活蛋白 1 (AP-1) 的结合位点高度相似的序列，事实上，该片段的 AP-1 序列对于佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (佛波醇) 或白细胞介素-1 的最大反应是必要的，但不足以实现。最大程度的诱导需要 AP-1 序列和基质溶素启动子的相邻上游调节序列 (URS) 之间的功能合作，这也是必要的，但还不够。我们证明 AP-1 序列和 URS 均结合佛波醇或 interieukln-1 诱导的核蛋白。 AP-1序列与溶基质素启动子中存在的另一序列的合作可能是一种通用机制，通过该机制，在许多启动子中发现的AP-1元件实现对各种刺激的最大且特异性的响应。
Interieukin-1, a mediator of inflammation, or tumor promoting phorbol esters induce transcription of stromelysin, a metalloproteinase that degrades extracellular matrix molecules and that is overexpressed in diseases such as rheumatoid arthritis. Sequences required for induction of transcription of the human stromelysin promoter are contained on a 46 base pair fragment. This fragment contains a sequence with a high degree of similarity to the binding site for the transcription factor activator protein-1 (AP-1) and indeed, the AP-1 sequence of this fragment is necessary but not sufficient for the maximal response to phorbol 12-myristate 13-acetate (phorbol) or interleukin-1. Maximal induction requires functional cooperation between the AP-1 sequence and a neighboring upstream regulatory sequence (URS) of the stromelysin promoter which is also necessary but not sufficient. We demonstrate that both the AP-1 sequence and the URS bind phorbol or interieukln-1 induced nuclear proteins. Cooperation of the AP-1 sequence with another sequence present in the stromelysin promoter may be a general mechanism whereby the AP-1 element, which is found in many promoters, achieves a maximal and specific response to various stimuli.