Abstract
Simple SummaryThe 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.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.
Highlights
The MNT transcription factor belongs to the MXD family, which shares a basic helix–loop–helix–leucine zipper domain as well as a SIN3 interaction domain (SID)
MNT represses transcription through direct interaction with the SIN3 proteins through the SID, a domain in the N-termini that binds to the SIN3 s paired amphipathic helix (PAH2)
Cancer Genome Atlas (TCGA) data, heterozygous MNT deletion was found in 10% of the tumors and in more than 20% of liver hepatocellular carcinomas, lung adenocarcinomas, sarcomas, and uterine carcinosarcomas [16]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. MNT is a unique member of the MXD family due to several features; it is (i) the largest protein of the family; (ii) the most divergent gene in its sequences; (iii) ubiquitously expressed in human tissues; (iv) essential for mouse development; (v) expressed in both quiescent and proliferating cells; (vi) altered in human cancer; and (vii) is frequently involved in tumorigenesis (Table 1). It plays an important role in modeling the oncogenic activities of MYC, as an antagonist in some models or as a cooperator in others (reviewed in [10])
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