Division of Hematology/Oncology, The Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
The Department of Microbiology and Molecular Genetics, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Cells. 2022 Feb 21;11(4):747. doi: 10.3390/cells11040747.
Among the first discovered and most prominent cellular oncogenes is which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six "Mxd proteins" (Mxd1-4, Mnt and Mga), each of which heterodimerizes with Max and largely opposes Myc's functions. More recently, a second group of bHLH-ZIP proteins (the Mlx Network) has emerged that bears many parallels with the Myc Network. It is comprised of the Myc-like factors ChREBP and MondoA, which, in association with the Max-like member Mlx, regulate smaller and more functionally restricted repertoires of target genes, some of which are shared with Myc. Opposing ChREBP and MondoA are heterodimers comprised of Mlx and Mxd1, Mxd4 and Mnt, which also structurally and operationally link the two Networks. We discuss here the functions of these "Extended Myc Network" members, with particular emphasis on their roles in suppressing normal and neoplastic growth. These roles are complex due to the temporal- and tissue-restricted expression of Extended Myc Network proteins in normal cells, their regulation of both common and unique target genes and, in some cases, their functional redundancy.
在最早发现的和最突出的细胞癌基因中，编码 bHLH-ZIP 转录因子（Myc），它既能激活又能抑制参与增殖、能量产生、代谢和翻译的众多基因。Myc 属于一小群 bHLH-ZIP 转录调节因子（Myc 网络），包括其必需的异二聚体化伴侣 Max 和六个“Mxd 蛋白”（Mxd1-4、Mnt 和 Mga），每个蛋白都与 Max 异二聚化，并在很大程度上反对 Myc 的功能。最近，出现了第二组 bHLH-ZIP 蛋白（Mlx 网络），与 Myc 网络有许多相似之处。它由 Myc 样因子 ChREBP 和 MondoA 组成，它们与 Max 样成员 Mlx 一起调节更小、功能更受限的靶基因谱，其中一些与 Myc 共享。与 ChREBP 和 MondoA 相对立的是由 Mlx 和 Mxd1、Mxd4 和 Mnt 组成的异二聚体，它们也在结构和操作上连接了这两个网络。我们在这里讨论这些“扩展 Myc 网络”成员的功能，特别强调它们在抑制正常和肿瘤生长中的作用。这些作用很复杂，因为在正常细胞中，扩展 Myc 网络蛋白的表达具有时间和组织特异性，它们调节共同和独特的靶基因，并且在某些情况下，它们具有功能冗余。
