{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Aminoacyl‐tRNA synthetase–interacting multifunctional protein 1 (AIMP1), also known as p43, was initially discovered as a component of the multi–tRNA synthetase complex involved in protein translation. However, a growing body of work has revealed that AIMP1 plays diverse noncanonical roles that span neurodevelopment, immune regulation, and tumor suppression. Genetic studies have demonstrated that deleterious mutations in AIMP1 are associated with hypomyelinating leukodystrophies and Pelizaeus‐Merzbacher–like disease, underscoring its pivotal function in maintaining axonal integrity and proper central nervous system development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to its intracellular function, AIMP1 can be proteolytically processed to release a secreted cytokine—endothelial monocyte–activating polypeptide II (EMAP II)—which exhibits potent proinflammatory and antiangiogenic activities. Secreted AIMP1/EMAP II has been shown to stimulate the maturation and activation of dendritic cells, thereby favoring a T helper 1 immune response through increased interleukin‐12 production."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Moreover, AIMP1 can modulate immune function by interacting directly with chaperones such as gp96 to regulate its endoplasmic reticulum retention and, consequently, dendritic cell activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In further support of its immunoregulatory role, studies have identified a specific receptor for full‐length AIMP1—CD23—through which AIMP1 prompts tumor necrosis factor–α secretion via ERK1/2 signaling, a property that distinguishes its activity from that of the C‐terminal EMAP II fragment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In the cancer context, AIMP1 expression is frequently reduced in tumor tissues"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", whereas treatment with recombinant AIMP1 has demonstrated significant antitumor efficacy by inducing the systemic release of tumor‐suppressing cytokines."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Beyond these functions, AIMP1 negatively regulates transforming growth factor–β signaling by stabilizing the E3 ligase Smurf2, thereby influencing cellular proliferation and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these studies indicate that AIMP1 is a multifunctional protein whose roles extend well beyond translation; it serves as a critical mediator in neural integrity, immune activation, and tumor suppression, acting both intracellularly as a signaling modulator and extracellularly as a cytokine."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Geneviève Bernard, Eliane Chouery, Maria Lisa Putorti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.07.014"}], "href": "https://doi.org/10.1016/j.ajhg.2011.07.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21855841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21855841"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Miora Feinstein, Barak Markus, Iris Noyman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pelizaeus-Merzbacher-like disease caused by AIMP1/p43 homozygous mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.10.016"}], "href": "https://doi.org/10.1016/j.ajhg.2010.10.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21092922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21092922"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sun Young Chang, Sang Gyu Park, Sunghoon Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of the C-terminal domain of p43 and the alpha subunit of ATP synthase. Its functional implication in endothelial cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M108792200"}], "href": "https://doi.org/10.1074/jbc.M108792200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11741979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11741979"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Matthias Clauss, Robert Voswinckel, Gangaraju Rajashekhar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke-induced emphysema in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI43881"}], "href": "https://doi.org/10.1172/JCI43881"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21576822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21576822"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eugene Kim, Seung Hyun Kim, Sunghoon Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AIMP1/p43 protein induces the maturation of bone marrow-derived dendritic cells with T helper type 1-polarizing ability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.180.5.2894"}], "href": "https://doi.org/10.4049/jimmunol.180.5.2894"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18292511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18292511"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jung Min Han, Sang Gyu Park, Bei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aminoacyl-tRNA synthetase-interacting multifunctional protein 1/p43 controls endoplasmic reticulum retention of heat shock protein gp96: its pathological implications in lupus-like autoimmune diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2007.061266"}], "href": "https://doi.org/10.2353/ajpath.2007.061266"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17525271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17525271"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hyuk-Sang Kwon, Min Chul Park, Dae Gyu Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of CD23 as a functional receptor for the proinflammatory cytokine AIMP1/p43."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.108209"}], "href": "https://doi.org/10.1242/jcs.108209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22767513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22767513"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sung Soo Kim, Soo Young Hur, Yoo Ri Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of AIMP1, 2 and 3, the scaffolds for the multi-tRNA synthetase complex, is downregulated in gastric and colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumori (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/030089161109700321"}], "href": "https://doi.org/10.1177/030089161109700321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21789020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21789020"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jung Min Han, Heejoon Myung, Sunghoon Kim "}, {"type": "b", "children": [{"type": "t", "text": "Antitumor activity and pharmacokinetic properties of ARS-interacting multi-functional protein 1 (AIMP1/p43)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2009.06.005"}], "href": "https://doi.org/10.1016/j.canlet.2009.06.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19573982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19573982"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yeon Sook Lee, Jung Min Han, Sung Hwa Son, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.04.099"}], "href": "https://doi.org/10.1016/j.bbrc.2008.04.099"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18448069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18448069"}]}]}]}