{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMAX functions as a pivotal transcriptional regulator in embryonic stem cells and germ cells, where it plays an essential role in maintaining pluripotency by repressing germ cell‐related genes and preventing premature meiotic onset. In these contexts, MAX—often acting as part of multi‐protein complexes that include epigenetic modifiers such as histone and DNA methyltransferases—ensures that the expression of germ cell‐specific transcripts remains tightly controlled until appropriate developmental cues are received. Indeed, in embryonic stem cells, loss or attenuation of MAX expression leads to the derepression of germ cell gene networks and the early induction of meiotic markers, underscoring its critical gatekeeping function in cell fate determination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in developmental biology, perturbations in MAX activity have significant implications in oncogenesis and metabolic regulation. In certain cancers such as small cell lung cancer, deletion of MAX can trigger metabolic rewiring—including enhanced serine and one‐carbon metabolism—that underpins tumor progression and can influence the response to nutrient depletion. Similarly, in hepatic cells exposed to toxic bile acids, the dynamic interplay between MYC–MAX and antagonistic complexes modulates the expression of key apoptosis and cell cycle regulators, linking MAX function to metabolic and stress-response pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMAX further serves as a critical cofactor in transcriptional networks through its interaction with MYC family proteins and other nuclear partners. In diverse cell types, including primary B lymphocytes and renal contexts, the formation of MYC–MAX heterodimers is vital for the fine-tuning of gene expression programs that govern cell proliferation, differentiation, and responses to extracellular cues. Partners such as hnRNP U have been implicated in modulating MYC–MAX-mediated transcriptional activation, while alterations in MAX-associated networks affect signaling pathways linked to cell cycle control and metabolic homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNote: Although the initial query mentioned PPP1R37, none of the provided abstracts discuss PPP1R37. The summaries above reflect the collective insights regarding MAX, which is extensively characterized across these studies.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ikuma Maeda, Daiji Okamura, Yuko Tokitake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Max is a repressor of germ cell-related gene expression in mouse embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms2780"}], "href": "https://doi.org/10.1038/ncomms2780"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23612295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23612295"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ayumu Suzuki, Masataka Hirasaki, Tomoaki Hishida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms11056"}], "href": "https://doi.org/10.1038/ncomms11056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27025988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27025988"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ayumu Suzuki, Masataka Hirasaki, Akihiko Okuda "}, {"type": "b", "children": [{"type": "t", "text": "Does MAX open up a new avenue for meiotic research?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Growth Differ (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/dgd.12344"}], "href": "https://doi.org/10.1111/dgd.12344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28220481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28220481"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Daiki Tatsumi, Yohei Hayashi, Mai Endo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0205969"}], "href": "https://doi.org/10.1371/journal.pone.0205969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30403691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30403691"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ayumu Suzuki, Kousuke Uranishi, Masazumi Nishimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAX controls meiotic entry in sexually undifferentiated germ cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-55506-7"}], "href": "https://doi.org/10.1038/s41598-024-55506-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38433229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38433229"}]}, {"type": "r", "ref": 6, "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": 7, "children": [{"type": "t", "text": "Arnaud Augert, Haritha Mathsyaraja, Ali H Ibrahim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAX Functions as a Tumor Suppressor and Rewires Metabolism in Small Cell Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2020.04.016"}], "href": "https://doi.org/10.1016/j.ccell.2020.04.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32470392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32470392"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kentaro Mochizuki, Jafar Sharif, Kenjiro Shirane, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-27345-x"}], "href": "https://doi.org/10.1038/s41467-021-27345-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34857746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34857746"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jun-Yi Zhu, Guanglei Wang, Xiaohu Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SARS-CoV-2 Nsp6 damages Drosophila heart and mouse cardiomyocytes through MGA/MAX complex-mediated increased glycolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-022-03986-6"}], "href": "https://doi.org/10.1038/s42003-022-03986-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36180527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36180527"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yoichiro Matsuoka, Norihisa Uehara, Airo Tsubura "}, {"type": "b", "children": [{"type": "t", "text": "hnRNP U interacts with the c-Myc-Max complex on the E-box promoter region inducing the ornithine decarboxylase gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2009)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19578763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19578763"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Junling Si, Xueyan Yu, Yingjie Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myc interacts with Max and Miz1 to repress C/EBPdelta promoter activity and gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-9-92"}], "href": "https://doi.org/10.1186/1476-4598-9-92"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20426839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20426839"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Mercedes Pérez-Olivares, Alfonsina Trento, Sara Rodriguez-Acebes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional interplay between c-Myc and Max in B lymphocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201845770"}], "href": "https://doi.org/10.15252/embr.201845770"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30126925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30126925"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Linxi Huang, Yuxuan Shi, Junjie Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated analysis of mRNA-seq and miRNA-seq reveals the potential roles of Egr1, Rxra and Max in kidney stone disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Urolithiasis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00240-022-01384-5"}], "href": "https://doi.org/10.1007/s00240-022-01384-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36484839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36484839"}]}]}]}