c-myc对肿瘤细胞生长抑制基因的转录调控

c-myc-mediated transcription repression of growth arrest genes in tumor cells

c-myc基因在许多肿瘤的发生、发展过程中起着重要作用,它主要通过对靶基因的转录调控发挥作用。对c-myc如何调节肿瘤细胞周期生长抑制基因转录机制进行综述。c-myc对细胞周期的调控主要通过对生长抑制基因转录抑制实现,主要有2个不同机制一个通过myc/Max二聚体中c-myc蛋白的羧基端(C末端)与Mil-1形成复合物与生长抑制基因p15等启动子Inr区域结合,拮抗其他转录激活因子如Mil-1与Inr结构结合。另一机制c-myc及可能存在的抑制物与转录激活因子Sp1及SMad(smaandmadhomologue)等形成复合物干扰Sp1等对生长抑制基因的激活。造成细胞恶性转化及增殖。

Expression of oncogene c-myc results in oncogenic activation and contributes to progression of a wide range of tumors, myc executes its multiple activities mostly through transcriptional regulation of the target genes. This paper reviews the mechanism of growth arrest gene transcription repression of cell cycle inhibitors by myc. It appears that myc repress growth arrest gene transcription by at lest two distinct mechanisms. One mechanism is limited to the binding of myc/Max heterodimers to the Inr element in their promoters and inhibition of Mil-1 or other transcriptional activator via the C-terminal domain of c-myc. The other mechanism is dependent on c-myc bingding to the Spl/SMad transcription factor via the c-myc repressed by c-myc and what other modes of c-myc transcriptional repression may exist. The ability of c-myc to repress transcription of growth arrest genes may contribute to its potential to promote proliferation and oncogenesis.