Yang-Yen H F, Chambard J C, Sun Y L, Smeal T, Schmidt T J, Drouin J, Karin M
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.
Cell. 1990 Sep 21;62(6):1205-15. doi: 10.1016/0092-8674(90)90396-v.
Glucocorticoids are potent inhibitors of collagenase induction by phorbol esters and inflammatory mediators. The target for this negative effect is the AP-1 site within the collagenase promoter, which also mediates its induction. Negative regulation is due to repression of AP-1 activity by the glucocorticoid receptor (GCR). While the GCR is a potent inhibitor of AP-1 activity (Jun/Fos), both c-Jun and c-Fos are potent repressors of GCR activity. In vitro experiments using purified GCR and c-Jun proteins suggest that mutual repression is due to direct interaction between the two. Direct interaction between GCR and either c-Jun or c-Fos is demonstrated by cross-linking and coimmunoprecipitation. These findings reveal a cross talk between two major signal transduction systems used to control gene transcription in response to extracellular stimuli, and a novel mechanism for transcriptional repression.
糖皮质激素是佛波酯和炎症介质诱导胶原酶的强效抑制剂。这种负面影响的靶点是胶原酶启动子内的AP-1位点，该位点也介导其诱导作用。负调控是由于糖皮质激素受体（GCR）对AP-1活性的抑制。虽然GCR是AP-1活性（Jun/Fos）的强效抑制剂，但c-Jun和c-Fos都是GCR活性的强效抑制剂。使用纯化的GCR和c-Jun蛋白进行的体外实验表明，相互抑制是由于两者之间的直接相互作用。通过交联和共免疫沉淀证明了GCR与c-Jun或c-Fos之间的直接相互作用。这些发现揭示了用于控制基因转录以响应细胞外刺激的两个主要信号转导系统之间的相互作用，以及一种新的转录抑制机制。
