Wasylyk C, Schneikert J, Wasylyk B
Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Oncogene. 1990 Jul;5(7):1055-8.
Cell transformation leads to alterations in both transcription and DNA replication. Activation of transcription by the expression of a number of transforming oncogenes is mediated by the transcription factor AP1 (Herrlich & Ponta, 1989; Imler & Wasylyk, 1989). AP1 is a composite transcription factor, consisting of members of the jun and fos gene-families. c-jun and c-fos are progenitors of oncogenes, suggestion that an important transcriptional event in cell transformation is altered activity of AP1, which may arise either indirectly by oncogene expression or directly by structural modification of AP1. We report here that the v-jun oncogene and its progenitor c-jun, as fusion proteins with the lex-A-repressor DNA binding domain, can activate DNA replication from the Polyoma virus (Py) origin of replication, linked to the lex-A operator. The transcription-activation region of v-jun is required for activation of replication. When excess v-jun is expressed in the cell, replication is inhibited or 'squelched'. These results suggest that one consequence of deregulated jun activity could be altered DNA replication and that there are similarities in the way v-jun activates replication and transcription.
细胞转化会导致转录和DNA复制发生改变。许多转化癌基因的表达所介导的转录激活是由转录因子AP1完成的（赫里希和蓬塔，1989年；伊姆勒和瓦西利克，1989年）。AP1是一种复合转录因子，由jun和fos基因家族的成员组成。c-jun和c-fos是癌基因的前身，这表明细胞转化过程中一个重要的转录事件是AP1活性的改变，这种改变可能是由癌基因表达间接引起的，也可能是由AP1的结构修饰直接导致的。我们在此报告，v-jun癌基因及其前身c-jun作为与lex-A阻遏物DNA结合结构域的融合蛋白，可以激活来自多瘤病毒（Py）复制起点的DNA复制，该起点与lex-A操纵基因相连。v-jun的转录激活区域是激活复制所必需的。当细胞中过量表达v-jun时，复制会受到抑制或“压制”。这些结果表明，jun活性失调的一个后果可能是DNA复制改变，并且v-jun激活复制和转录的方式存在相似之处。
