Coussens L M, Yokoyama K, Chiu R
Department of Biological Chemistry, University of California, Los Angeles 90024-1782.
J Cell Physiol. 1994 Sep;160(3):435-44. doi: 10.1002/jcp.1041600306.
Transforming growth factor beta (TGF-beta), a multifunctional polypeptide growth factor, regulates the expression of many genes critical to cell cycle progression, such as members of the jun gene family which encode components of the transcription factor complex AP-1. The transforming proteins encoded by the early region 1A of adenovirus12 (Ad.12-E1A) abrogate some of the cellular responses to TGF-beta as well as affecting, differentially, the expression of cellular jun genes. Our data demonstrate that expression of Ad.12-E1A in rat 3Y1 fibroblast cells inhibits induction of junB by TGF-beta 1 while not altering the regulation of junB by phorbol ester or serum. Regulation of c-jun gene expression by TGF-beta 1, phorbol ester, and serum is not appreciably altered by the expression of Ad.12-E1A. Inhibition of TGF-beta induced junB expression is not due to a defect in TGF-beta/receptor interaction on Ad.12-E1A transformed cells and is not observed in other isotypic fibroblast cells transformed by SV40 or polyomavirus. These data suggest that multiple, independent, intracellular signal transduction pathways exist which mediate genomic responses to TGF-beta. Cellular expression of Ad.12-E1A-12S gene products results in selective disruption of some TGF-beta 1 signaling cascades and not those activated by phorbol ester or serum. These data further suggest that some cellular targets which mediate TGF-beta 1 action may also be unique targets of action for the E1A-12S transforming protein of adenovirus12.
转化生长因子β（TGF-β）是一种多功能多肽生长因子，可调节许多对细胞周期进程至关重要的基因的表达，例如编码转录因子复合物AP-1组分的jun基因家族成员。腺病毒12早期区域1A（Ad.12-E1A）编码的转化蛋白消除了细胞对TGF-β的一些反应，并不同程度地影响细胞jun基因的表达。我们的数据表明，Ad.12-E1A在大鼠3Y1成纤维细胞中的表达抑制了TGF-β1对junB的诱导，而不改变佛波酯或血清对junB的调节。Ad.12-E1A的表达并未明显改变TGF-β1、佛波酯和血清对c-jun基因表达的调节。对TGF-β诱导的junB表达的抑制并非由于Ad.12-E1A转化细胞上TGF-β/受体相互作用的缺陷，在由SV40或多瘤病毒转化的其他同型成纤维细胞中也未观察到这种抑制。这些数据表明，存在多种独立的细胞内信号转导途径介导对TGF-β的基因组反应。Ad.12-E1A-12S基因产物的细胞表达导致一些TGF-β1信号级联的选择性破坏，而不是由佛波酯或血清激活的信号级联。这些数据进一步表明，一些介导TGF-β1作用的细胞靶点也可能是腺病毒12的E1A-12S转化蛋白的独特作用靶点。
