Dooley S, Wundrack I, Blin N, Welter C
Department of Human Genetics, Univ of Saarland, Homburg, Germany.
Biochem Biophys Res Commun. 1995 Aug 24;213(3):789-95. doi: 10.1006/bbrc.1995.2199.
The c-Myc protein is involved in cellular transformation and mitogenesis, but also works as a potent inducer of differentiation and programmed cell death. Max as an obligate heterodimeric partner for Myc mediates its functions as a specific transcriptional activator and a transforming protein. Mad and Mxi1 proteins both heterodimerize with Max and compete with each other for limiting amounts of Max. Transcriptional activation by Myc can be suppressed by increasing the amount of Mad or Mxi1. This report shows the expression pattern of these Myc related factors at the mRNA level in a small cell lung cancer (SCLC) cell line (GLC4) which is characterized by c-myc amplification and strong constitutive c-myc overexpression. We found these genes transcriptionally active but uninfluenced from high c-myc transcription. Max was constantly transcribed at a relatively low level during cell cycle progression. Mad and mxi1 mRNA was at a surprisingly high level in proliferating cells. Mad was further upregulated and mxi1 was downregulated to basal levels during serum starvation of the cells. We further analyzed the activity of c-fos, c-jun, c-myb and nm23 which are described to be involved in c-myc transcriptional activation, c-jun and c-fos were not constitutively activated and can be excluded as regulators. High steady state c-myc in contrast influences the serum stimulated transient activation mechanism of these two genes. We identified high copy number nm23 mRNA whose role as a putative c-myc transcriptional activator is under investigation. Our results indicate that constitutive overexpression of c-myc does not require the activity of the nuclear oncogenes tested and that the m-RNA expression pattern of functionally related proteins is not influenced.
c-Myc蛋白参与细胞转化和有丝分裂原生成，同时也是分化和程序性细胞死亡的有效诱导剂。Max作为Myc的 obligate异二聚体伴侣，介导其作为特定转录激活因子和转化蛋白的功能。Mad和Mxi1蛋白都与Max形成异二聚体，并相互竞争有限量的Max。增加Mad或Mxi1的量可抑制Myc的转录激活。本报告显示了这些Myc相关因子在小细胞肺癌（SCLC）细胞系（GLC4）mRNA水平的表达模式，该细胞系的特征是c-myc扩增和强烈的组成型c-myc过表达。我们发现这些基因具有转录活性，但不受高c-myc转录的影响。在细胞周期进程中，Max持续以相对较低的水平转录。Mad和mxi1 mRNA在增殖细胞中的水平出奇地高。在细胞血清饥饿期间，Mad进一步上调，而mxi1下调至基础水平。我们进一步分析了c-fos、c-jun、c-myb和nm23的活性，这些基因被认为参与c-myc转录激活，c-jun和c-fos未被组成型激活，可以排除作为调节因子。相比之下，高稳态c-myc影响这两个基因的血清刺激瞬时激活机制。我们鉴定出高拷贝数的nm23 mRNA，其作为假定的c-myc转录激活因子的作用正在研究中。我们的结果表明，c-myc的组成型过表达不需要所测试的核癌基因的活性，并且功能相关蛋白的mRNA表达模式不受影响。
