Wei P, Vedeckis W V
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Endocrine. 1997 Dec;7(3):303-10. doi: 10.1007/BF02801323.
The glucocorticoid receptor (GR) is a ligand-activated nuclear transcription factor, and AP- 1 (Fos/Jun or Jun/Jun) is a transcription factor whose components are nuclear proteins encoded by c-fos and c-jun protooncogenes. Serum stimulation of serum-starved NIH 3T3 cells resulted in an approx 188-fold induction of c-fos mRNA at 30 min and an approximately ninefold induction of c-jun mRNA at 1 h, followed by an increase in GR mRNA levels at 3-12 hour (twofold). Sequential induction of cFos, cJun, and GR protein levels also occurred. Overexpression of the cFos protein in NIH 3T3 cells (NIH 3T3 [cFos 3] and NIH 3T3 [cFos 10]) caused an increase in the endogenous GR protein. Previous and present studies showed that a putative AP-1 site within the GR promoter binds AP-1 proteins (both Jun and Fos family members). To address the molecular mechanism involved in transcriptional activation of the GR gene, we investigated the relevance of AP-1 binding complexes in this activation and in overall regulation of GR gene transcription. Transient transfection with a full length GR promoter linked to a luciferase gene into both NIH 3T3 (cFos 3) and NIH 3T3 (cFos 10) cells gave rise to an induction of luciferase activity. This induction was abolished following mutation or deletion of the GR AP-1 site from the promoter. These findings suggest that cFos is responsible for the induction of GR expression in serum-stimulated NIH 3T3 cells, and serum growth factors may stimulate GR transcription by a cFos-dependent mechanism at the putative AP-1 site. These studies support a role for the AP-1 transcription factor in regulating GR gene expression.
糖皮质激素受体（GR）是一种配体激活的核转录因子，而AP-1（Fos/Jun或Jun/Jun）是一种转录因子，其组分是由原癌基因c-fos和c-jun编码的核蛋白。血清饥饿的NIH 3T3细胞经血清刺激后，在30分钟时c-fos mRNA诱导约188倍，在1小时时c-jun mRNA诱导约9倍，随后在3至12小时GR mRNA水平增加（两倍）。cFos、cJun和GR蛋白水平也依次诱导。NIH 3T3细胞（NIH 3T3 [cFos 3]和NIH 3T3 [cFos 10]）中cFos蛋白的过表达导致内源性GR蛋白增加。既往和目前的研究表明，GR启动子内一个假定的AP-1位点结合AP-1蛋白（Jun和Fos家族成员）。为了探讨GR基因转录激活所涉及的分子机制，我们研究了AP-1结合复合物在这种激活以及GR基因转录总体调控中的相关性。将与荧光素酶基因相连的全长GR启动子瞬时转染到NIH 3T3（cFos 3）和NIH 3T3（cFos 10）细胞中，导致荧光素酶活性诱导。从启动子中突变或缺失GR AP-1位点后，这种诱导被消除。这些发现表明，cFos负责血清刺激的NIH 3T3细胞中GR表达的诱导，血清生长因子可能通过cFos依赖机制在假定的AP-1位点刺激GR转录。这些研究支持AP-1转录因子在调节GR基因表达中的作用。
