{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMNT is a member of the Myc/Max/Mad network of transcription factors that functions predominantly as a transcriptional repressor. By forming heterodimers with MAX and, under certain conditions, with MLX or even as homodimers, MNT binds to E‐box sequences in target gene promoters to counterbalance the activating effects of Myc. This antagonism plays a critical role in regulating cell proliferation, differentiation, and survival, as well as in maintaining cell cycle control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several contexts, a dynamic balance between MNT and Myc activities underpins cellular decision making. In hepatocytes exposed to toxic bile acids, for example, a decline in MNT expression coupled with a switch toward Myc–Max binding leads to up‐regulation of pro‐apoptotic factors such as p53 and cyclin D1, promoting apoptosis. Similarly, studies in lymphocytes reveal that MNT is upregulated during activation to protect against Myc‐dependent apoptosis, emphasizing its function as an essential buffer against unchecked proliferative signaling. Furthermore, in neuroblastoma models, although changes in MNT levels are modest compared to Myc downregulation during differentiation, the presence of MNT continues to contribute to an equilibrium critical for proper cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates MNT in modulating other pivotal processes. In hepatocellular carcinoma cells, differential expression of MNT affects migration, suggesting a role in tumor dispersal. In the context of breast cancer, MNT is essential for epithelial-to-mesenchymal transition by recruiting histone deacetylase 1 (HDAC1) to repress epithelial identity genes, thereby facilitating a mesenchymal phenotype. Moreover, in lung adenocarcinoma, MNT has been shown to promote cell proliferation and diminish chemotherapy sensitivity by binding to and repressing the promoter of SAT1, a gene involved in the ferroptosis pathway. Finally, epigenetic studies in monocytes from patients with chronic kidney disease indicate that uremia-induced methylation dysregulation affects transcription regulators including MNT, contributing to aberrant monocyte differentiation. Collectively, these findings underscore that tight regulation of MNT, whether through its dimerization with MAX or alternative interactions, is critical for controlling gene expression programs that govern proliferation, apoptosis, migration, and cell fate decisions – processes of both physiological and pathological significance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anna Grynfeld Smith, Nikita Popov, Martha Imreh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and DNA-binding activity of MYCN/Max and Mnt/Max during induced differentiation of human neuroblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.20121"}], "href": "https://doi.org/10.1002/jcb.20121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15258910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15258910"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Therese Wahlström, Marie Henriksson "}, {"type": "b", "children": [{"type": "t", "text": "Mnt takes control as key regulator of the myc/max/mxd network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0065-230X(06)97003-1"}], "href": "https://doi.org/10.1016/S0065-230X(06"}, {"type": "t", "text": "97003-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17419941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17419941"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Martin Montagne, Jean-François Naud, Pierre Lavigne "}, {"type": "b", "children": [{"type": "t", "text": "Elucidation of the structural determinants responsible for the specific formation of heterodimeric Mxd1/Max b-HLH-LZ and its binding to E-box sequences."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2007.11.062"}], "href": "https://doi.org/10.1016/j.jmb.2007.11.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18155722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18155722"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Heping Yang, Tony W H Li, Kwang Suk Ko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Switch from Mnt-Max to Myc-Max induces p53 and cyclin D1 expression and apoptosis during cholestasis in mouse and human hepatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.22720"}], "href": "https://doi.org/10.1002/hep.22720"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19086036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19086036"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qi Zhou, Tao Huang, Ya-feng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of Max binding protein as a novel binding protein of Nck1 and characterization of its role in inhibiting human liver cancer SK-HEP-1 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chin Med J (Engl) (2012)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22964333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22964333"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Therese Wahlström, Sergey Belikov, Marie Arsenian Henriksson "}, {"type": "b", "children": [{"type": "t", "text": "Chromatin dynamics at the hTERT promoter during transcriptional activation and repression by c-Myc and Mnt in Xenopus leavis oocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2013.07.004"}], "href": "https://doi.org/10.1016/j.yexcr.2013.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23860446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23860446"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jason M Link, Peter J Hurlin "}, {"type": "b", "children": [{"type": "t", "text": "The activities of MYC, MNT and the MAX-interactome in lymphocyte proliferation and oncogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2014.04.004"}], "href": "https://doi.org/10.1016/j.bbagrm.2014.04.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24731854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24731854"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Adam M Zawada, Jenny S Schneider, Anne I Michel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation profiling reveals differences in the 3 human monocyte subsets and identifies uremia to induce DNA methylation changes during differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15592294.2016.1158363"}], "href": "https://doi.org/10.1080/15592294.2016.1158363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27018948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27018948"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "M Carmen Lafita-Navarro, Judit Liaño-Pons, Andrea Quintanilla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.010389"}], "href": "https://doi.org/10.1074/jbc.RA119.010389"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31919096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31919096"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Deborah P Lavin, Leila Abassi, Mohammed Inayatullah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mnt Represses Epithelial Identity To Promote Epithelial-to-Mesenchymal Transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00183-21"}], "href": "https://doi.org/10.1128/MCB.00183-21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34460331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34460331"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Guangyin Zhao, Jiaqi Liang, Yuchen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MNT inhibits lung adenocarcinoma ferroptosis and chemosensitivity by suppressing SAT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-024-06373-5"}], "href": "https://doi.org/10.1038/s42003-024-06373-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38831092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38831092"}]}]}]}