Facchini L M, Penn L Z
Ontario Cancer Institute/Princess Margaret Hospital, Department of Medical Biophysics, University of Toronto, Canada.
FASEB J. 1998 Jun;12(9):633-51.
A major dilemma facing the Myc researcher is understanding how c-Myc regulation of gene transcription translates into the proliferative and oncogenic activities mediated by c-Myc protein. Indeed, much effort has focused on attempting to link c-Myc activation of gene transcription with both cell cycle progression and transformation mechanisms. Considerable progress has been made in recent years, with the identification of new Myc binding proteins as well as novel cellular targets of Myc-Max complexes. These discoveries have yielded more than a few surprises and challenged those working in the field to rethink traditional paradigms. It is now evident that c-Myc can also repress the transcription of specific genes, and Myc-mediated repression appears to be linked to Myc-dependent transformation. We summarize the evidence on Myc biological and molecular functions with regard to Myc-Max transcriptional regulation. In addition, we reevaluate current models of Myc transcriptional modulation in light of the discovery of new Myc binding partners and novel downstream target genes. Finally, we explore whether direct transactivation of cellular genes by Myc-Max heterodimers is sufficient for the growth-promoting and transforming activities of Myc or whether other molecular activities of Myc, such as Myc-mediated repression, may play a key role.
Myc研究人员面临的一个主要困境是理解c-Myc对基因转录的调控如何转化为由c-Myc蛋白介导的增殖和致癌活性。事实上，很多努力都集中在试图将c-Myc对基因转录的激活与细胞周期进程和转化机制联系起来。近年来已经取得了相当大的进展，鉴定出了新的Myc结合蛋白以及Myc-Max复合物的新细胞靶点。这些发现带来了不少惊喜，并促使该领域的研究人员重新思考传统范式。现在很明显，c-Myc也可以抑制特定基因的转录，并且Myc介导的抑制似乎与Myc依赖性转化有关。我们总结了关于Myc-Max转录调控方面Myc生物学和分子功能的证据。此外，鉴于新的Myc结合伙伴和新的下游靶基因的发现，我们重新评估了当前Myc转录调控模型。最后，我们探讨Myc-Max异二聚体对细胞基因的直接反式激活是否足以实现Myc的促生长和转化活性，或者Myc的其他分子活性，如Myc介导的抑制，是否可能起关键作用。
