The Multiple Faces of MNT and Its Role as a MYC Modulator

SIMPLE SUMMARY: The MYC oncoprotein is deregulated in up to 70% of human tumors and has a crucial role in the initiation, progression, and maintenance of the tumorigenic process. The MYC modulator MNT belongs to the MXD family of MYC antagonists and transcriptional repressors. It differs from the other MXD family members due to its essential role in the cell and its diverse and complex functions that can either facilitate or impair MYC-driven tumorigenesis. As MYC is a difficult therapeutic target, increasing our knowledge of other proteins in the MYC network will provide the basis for alternative strategies to impair MYC activity in cancer. ABSTRACT: MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.