Berko-Flint Y, Levkowitz G, Vardimon L
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel.
EMBO J. 1994 Feb 1;13(3):646-54. doi: 10.1002/j.1460-2075.1994.tb06303.x.
The ability of the glucocorticoid receptor (GR) to induce gene expression in embryonic chicken retinal tissue increases dramatically during development, although the quantity of the receptor molecules does not change greatly with age. This study examines the possible involvement of c-Jun in the developmental control of GR activity. Expression of c-Jun in retinal tissue was high at early embryonic ages and declined during development. Elevation of c-Jun expression in retina of mid-developmental ages by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or by introduction of a c-Jun expression vector, caused a pronounced decline in the inducibility of the endogenous glutamine synthetase gene and the transiently transfected CAT constructs p delta G46TCO and pGS2.1CAT, that are controlled by a minimal consensus glucocorticoid response element (GRE) promoter and the glutamine synthetase promoter, respectively. The effect of c-Jun was dose dependent and could be reversed by overexpression of GR. C-Jun-evoked repression of GR activity could be relieved by overexpression of Jun D. Overexpression of Jun D could also elevate the responsiveness of early embryonic retina to glucocorticoids and cause a 5-fold increase in p delta G46TCO induction. The effect of Jun D could be reversed by overexpression of c-Jun. Expression of c-Jun might therefore be important for repression of GR activity at early embryonic ages.
糖皮质激素受体(GR)在胚胎期鸡视网膜组织中诱导基因表达的能力在发育过程中显著增强,尽管受体分子的数量并不会随年龄增长而发生很大变化。本研究探讨了c-Jun在GR活性发育调控中可能发挥的作用。c-Jun在视网膜组织中的表达在胚胎早期较高,并在发育过程中下降。通过用12-氧-十四烷酰佛波醇-13-乙酸酯(TPA)处理,或通过导入c-Jun表达载体,使发育中期视网膜中c-Jun表达升高,导致内源性谷氨酰胺合成酶基因以及瞬时转染的CAT构建体pδG46TCO和pGS2.1CAT的诱导性显著下降,它们分别由最小共有糖皮质激素反应元件(GRE)启动子和谷氨酰胺合成酶启动子控制。c-Jun的作用呈剂量依赖性,并且可以通过GR的过表达来逆转。Jun D的过表达可以缓解c-Jun引起的GR活性抑制。Jun D的过表达还可以提高早期胚胎视网膜对糖皮质激素的反应性,并使pδG46TCO诱导增加5倍。Jun D的作用可以通过c-Jun的过表达来逆转。因此,c-Jun的表达可能对胚胎早期GR活性的抑制很重要。