Diolaiti Daniel, McFerrin Lisa, Carroll Patrick A, Eisenman Robert N
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, USA.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, USA.
Biochim Biophys Acta. 2015 May;1849(5):484-500. doi: 10.1016/j.bbagrm.2014.05.016. Epub 2014 May 22.
The transcription factor MYC and its related family members MYCN and MYCL have been implicated in the etiology of a wide spectrum of human cancers. Compared to other oncoproteins, such as RAS or SRC, MYC is unique because its protein coding region is rarely mutated. Instead, MYC's oncogenic properties are unleashed by regulatory mutations leading to unconstrained high levels of expression. Under both normal and pathological conditions MYC regulates multiple aspects of cellular physiology including proliferation, differentiation, apoptosis, growth and metabolism by controlling the expression of thousands of genes. How a single transcription factor exerts such broad effects remains a fascinating puzzle. Notably, MYC is part of a network of bHLHLZ proteins centered on the MYC heterodimeric partner MAX and its counterpart, the MAX-like protein MLX. This network includes MXD1-4, MNT, MGA, MONDOA and MONDOB proteins. With some exceptions, MXD proteins have been functionally linked to cell cycle arrest and differentiation, while MONDO proteins control cellular metabolism. Although the temporal expression patterns of many of these proteins can differ markedly they are frequently expressed simultaneously in the same cellular context, and potentially bind to the same, or similar DNA consensus sequence. Here we review the activities and interactions among these proteins and propose that the broad spectrum of phenotypes elicited by MYC deregulation is intimately connected to the functions and regulation of the other network members. Furthermore, we provide a meta-analysis of TCGA data suggesting that the coordinate regulation of the network is important in MYC driven tumorigenesis. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
转录因子MYC及其相关家族成员MYCN和MYCL与多种人类癌症的病因有关。与其他癌蛋白（如RAS或SRC）相比，MYC具有独特性，因为其蛋白质编码区域很少发生突变。相反，MYC的致癌特性是由调控突变释放出来的，这些突变导致其不受限制地高水平表达。在正常和病理条件下，MYC通过控制数千个基因的表达来调节细胞生理的多个方面，包括增殖、分化、凋亡、生长和代谢。单个转录因子如何发挥如此广泛的作用仍然是一个引人入胜的谜题。值得注意的是，MYC是一个以MYC异二聚体伴侣MAX及其对应物MAX样蛋白MLX为中心的bHLHLZ蛋白网络的一部分。这个网络包括MXD1 - 4、MNT、MGA、MONDOA和MONDOB蛋白。除了一些例外情况，MXD蛋白在功能上与细胞周期停滞和分化有关，而MONDO蛋白则控制细胞代谢。尽管这些蛋白中的许多蛋白的时间表达模式可能有显著差异，但它们经常在相同的细胞环境中同时表达，并可能结合相同或相似的DNA共有序列。在这里，我们综述了这些蛋白之间的活性和相互作用，并提出MYC失调引发的广泛表型与其他网络成员的功能和调控密切相关。此外，我们对TCGA数据进行了荟萃分析，表明该网络的协同调控在MYC驱动的肿瘤发生中很重要。本文是名为“细胞生物学和病理学中的Myc蛋白”的特刊的一部分。
