The Mlx network: evidence for a parallel Max-like transcriptional network that regulates energy metabolism

Abstract

Recent experiments suggest the existence of a transcriptional network that functions in parallel to the canonical Myc/Max/Mad transcriptional network. Unlike the Myc/Max/Mad network, our understanding of this network is still in its infancy. At the center of this network is a Max-like protein called Mlx; hence we have called this network the Mlx network. Like Max, Mix interacts with transcriptional repressors and transcriptional activators, namely the Mad family and the Mondo family, respectively. Similar to Max-containing heterodimers, Mlx-containing heterodimers recognize CACGTG E-box elements, suggesting that the transcriptional targets of these two networks may overlap. Supporting this hypothesis, we have observed genetic interactions between the Drosophila melanogaster orthologs of Myc and Mondo. In higher eukaryotes, two proteins, MondoA and MondoB/CHREBP/WBSCR14, constitute the Mondo family. At present little is known about the transcriptional targets of MondoA; however, pyruvate kinase is a putative target of MondoB/CHREBP/WBSCR14, suggesting a function for the Mondo family in glucose and/or lipid metabolism. Finally, unlike the predominant nuclear localization of Myc family proteins, both Mondo family members localize to the cytoplasm. Therefore, while the Myc and Mondo families may share some biological functions, it is likely each family is under distinct regulatory control.