{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n S‐adenosylmethionine decarboxylase 1 (AMD1) is a pivotal enzyme in the polyamine biosynthetic pathway that catalyzes the decarboxylation of S‐adenosylmethionine (SAM) to generate decarboxylated SAM (dcSAM), the essential aminopropyl donor for the synthesis of the polyamines spermidine and spermine. Several studies have demonstrated that AMD1 plays an integral role in coupling cellular metabolism with growth and differentiation. For example, in neuroblastoma, AMD1 is coordinately deregulated along with other key polyamine enzymes under MYCN‐driven oncogenesis, contributing to tumor cell growth and malignant progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, the stability of AMD1 is controlled by mTORC1 signalling, thereby translating growth cues into enhanced polyamine flux that supports oncogenic proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic ablation studies in mice reveal that AMD1 activity is indispensable for early embryonic development; embryos lacking AMD1 fail to progress beyond early stages, highlighting its essential role in cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, a unique translational stalling mechanism operating on the AMD1 mRNA limits the number of enzyme molecules produced from a single transcript, suggesting an autoregulatory “counting” system that safeguards against dysregulated polyamine synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of stem cell biology, AMD1 is critical for maintaining embryonic stem cell self‐renewal by influencing MYC expression levels and preserving the polyamine pool required for sustained proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In human cancers, elevated AMD1 expression has been implicated in enhanced tumor aggressiveness. For instance, in hepatocellular carcinoma increased AMD1 not only augments polyamine synthesis but also promotes cancer stem cell characteristics through pathways involving mRNA demethylation and protein interactions, correlating with poorer prognoses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, in gastric cancer, AMD1 overexpression is associated with larger tumor size, invasive features, and shorter overall survival, with AMD1 knockdown inhibiting cell proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond cancer, genetic studies have linked variants in AMD1 to metabolic disturbances such as childhood obesity and altered plasma leptin levels, indicating that AMD1’s regulation of polyamine metabolism also impacts energy homeostasis and adiposity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, AMD1 functions as a key metabolic integrator by modulating polyamine flux and thereby influencing cell growth, differentiation, and oncogenesis. Its tightly regulated activity—ranging from translational control mechanisms to pathway stabilization via mTORC1—underscores its importance as a potential therapeutic target in diverse disease contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael D Hogarty, Murray D Norris, Kimberly Davis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-6866"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-6866"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19047152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19047152"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Natalia Martín-Martín, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature22964"}], "href": "https://doi.org/10.1038/nature22964"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28658205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28658205"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kazuhiro Nishimura, Fubito Nakatsu, Keiko Kashiwagi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1356-9597.2001.00494.x"}], "href": "https://doi.org/10.1046/j.1356-9597.2001.00494.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11856372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11856372"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Martina M Yordanova, Gary Loughran, Alexander V Zhdanov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature25174"}], "href": "https://doi.org/10.1038/nature25174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29310120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29310120"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dawei Zhang, Tianyun Zhao, Haw Siang Ang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.182998.111"}], "href": "https://doi.org/10.1101/gad.182998.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22391449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22391449"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xinyu Bian, Dongmin Shi, Kailin Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMD1 upregulates hepatocellular carcinoma cells stemness by FTO mediated mRNA demethylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Transl Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ctm2.352"}], "href": "https://doi.org/10.1002/ctm2.352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33783988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33783988"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lijiao Xu, Xue You, Qianqian Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgz098"}], "href": "https://doi.org/10.1093/carcin/bgz098"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31140554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31140554"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rubina Tabassum, Alok Jaiswal, Ganesh Chauhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variant of AMD1 is associated with obesity in urban Indian children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0033162"}], "href": "https://doi.org/10.1371/journal.pone.0033162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22496743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22496743"}]}]}]}