Wahlström Therese, Henriksson Marie
Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Adv Cancer Res. 2007;97:61-80. doi: 10.1016/S0065-230X(06)97003-1.
Myc is the most frequently deregulated oncogene in human tumors. The protein belongs to the Myc/Max/Mxd network of transcriptional regulators important for cell growth, proliferation, differentiation, and apoptosis. The ratio between Mnt/Max and c-Myc/Max on the 5'-CACGTG-3' E-box sequence at shared target genes is of great importance for cell cycle progression and arrest. Serum stimulation of quiescent cells results in phosphorylation of Mnt and disruption of the critical Mnt-mSin3-HDAC1 interaction. This in turn leads to increased expression of the Myc/Mnt target gene cyclin D2. It is therefore possible that Myc function relies on its ability to overcome transcriptional repression by Mnt and that relief of Mnt-mediated transcriptional repression is of greater importance for regulation of target genes than the sole activation by Myc. In addition, Mnt has many features of a tumor suppressor and may thus be nonfunctional or inactivated in human tumors. In summary, accumulating evidence supports the model of Mnt as the key regulator of the network in vivo.
Myc是人类肿瘤中最常发生失调的癌基因。该蛋白属于转录调节因子的Myc/Max/Mxd网络，对细胞生长、增殖、分化和凋亡至关重要。在共享靶基因的5'-CACGTG-3' E-box序列上，Mnt/Max与c-Myc/Max的比例对细胞周期进程和停滞非常重要。血清刺激静止细胞会导致Mnt磷酸化，并破坏关键的Mnt-mSin3-HDAC1相互作用。这进而导致Myc/Mnt靶基因细胞周期蛋白D2的表达增加。因此，Myc的功能可能依赖于其克服Mnt转录抑制的能力，并且Mnt介导的转录抑制的解除对靶基因的调控可能比Myc的单独激活更为重要。此外，Mnt具有许多肿瘤抑制因子的特征，因此在人类肿瘤中可能无功能或失活。总之，越来越多的证据支持Mnt作为体内该网络关键调节因子的模型。
