Hann Stephen R
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175.
Cold Spring Harb Perspect Med. 2014 Jun 17;4(9):a014399. doi: 10.1101/cshperspect.a014399.
The transcription factor MYC has fundamental roles in proliferation, apoptosis, tumorigenesis, and stem cell pluripotency. Over the last 30 years extensive information has been gathered on the numerous cofactors that interact with MYC and the target genes that are regulated by MYC as a means of understanding the molecular mechanisms controlling its diverse roles. Despite significant advances and perhaps because the amount of information learned about MYC is overwhelming, there has been little consensus on the molecular functions of MYC that mediate its critical biological roles. In this perspective, the major MYC cofactors that regulate the various transcriptional activities of MYC, including canonical and noncanonical transactivation and transcriptional repression, will be reviewed and a model of how these transcriptional mechanisms control MYC-mediated proliferation, apoptosis, and tumorigenesis will be presented. The basis of the model is that a variety of cofactors form dynamic MYC transcriptional complexes that can switch the molecular and biological functions of MYC to yield a diverse range of outcomes in a cell-type- and context-dependent fashion.
转录因子MYC在细胞增殖、凋亡、肿瘤发生和干细胞多能性方面发挥着重要作用。在过去30年里，人们收集了大量关于与MYC相互作用的众多辅因子以及受MYC调控的靶基因的信息，以此来理解控制其多种作用的分子机制。尽管取得了重大进展，或许也正是因为关于MYC的信息量过于庞大，对于介导其关键生物学作用的MYC分子功能，目前几乎没有达成共识。从这个角度出发，本文将综述调控MYC各种转录活性（包括经典和非经典反式激活以及转录抑制）的主要MYC辅因子，并提出一个关于这些转录机制如何控制MYC介导的细胞增殖、凋亡和肿瘤发生的模型。该模型的基础是，多种辅因子形成动态的MYC转录复合物，这些复合物可以切换MYC的分子和生物学功能，从而以细胞类型和环境依赖的方式产生多种不同的结果。
