{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein N‑terminal acetylation is a widespread co‑translational modification critical for regulating protein stability, localization, and interactions. The NatB complex, which is responsible for acetylating 15–20% of the proteome, is composed of a catalytic subunit—known in vertebrates as NAA20 (or by alternative nomenclature in some studies)—and one or more auxiliary subunits. In yeast and human cellular models, NatB-mediated acetylation has been linked to the proper structural organization of actomyosin fibers and is required for effective cellular migration, thus underscoring the functional significance of this enzyme complex in normal cell physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nMolecular investigations have further revealed that the assembly and activity of the NatB complex are governed by precise N‑terminal processing events. Specifically, the removal of the initiator methionine by methionine aminopeptidases exposes a conserved small, uncharged residue at position two—a requirement that is essential for NAA20 to stably interact with its partner subunit. Disruptions in this processing, whether by deletion or alteration of the critical amino acid, impair complex formation and consequently reduce the catalytic efficiency of NAA20 in substrate acetylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n \nDysregulation of NAA20 function has been implicated in several human diseases. In hepatocellular carcinoma, for instance, overexpression of NAA20 drives tumorigenesis by acetylating LKB1, which in turn attenuates AMPK activation and promotes mTOR‐dependent cell proliferation and autophagy. In triple‑negative breast cancer, increased NAA20 expression enhances EGFR signaling via a Rab5A‐mediated mechanism, leading to increased cell viability, migration, and invasion. Moreover, genetic studies have identified recessive missense variants in NAA20, linking its aberrant function to overlapping clinical phenotypes, while NatB‐catalyzed N‑terminal acetylation of proteins such as alpha‑synuclein protects them from proteasomal degradation—findings that pave the way for therapeutic strategies in neurodegenerative diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kristian K Starheim, Thomas Arnesen, Darina Gromyko, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Maturation of NAA20 Aminoterminal End Is Essential to Assemble NatB N-Terminal Acetyltransferase Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2020.09.010"}], "href": "https://doi.org/10.1016/j.jmb.2020.09.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32976911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32976911"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Taek-Yeol Jung, Jae-Eun Ryu, Mi-Mi Jang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Naa20, the catalytic subunit of NatB complex, contributes to hepatocellular carcinoma by regulating the LKB1-AMPK-mTOR axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s12276-020-00525-3"}], "href": "https://doi.org/10.1038/s12276-020-00525-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33219302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33219302"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jennifer Morrison, Norah K Altuwaijri, Kirsten Brønstad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense NAA20 variants impairing the NatB protein N-terminal acetyltransferase cause autosomal recessive developmental delay, intellectual disability, and microcephaly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41436-021-01264-0"}], "href": "https://doi.org/10.1038/s41436-021-01264-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34230638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34230638"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lei Qiao, Chao Dong, Wenlei Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NAA20 recruits Rin2 and promotes triple-negative breast cancer progression by regulating Rab5A-mediated activation of EGFR signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2023.110922"}], "href": "https://doi.org/10.1016/j.cellsig.2023.110922"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37827343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37827343"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Saranya Santhosh Kumar, Nima N Naseri, Sarshan R Pather, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.adj4767"}], "href": "https://doi.org/10.1126/sciadv.adj4767"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38335281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38335281"}]}]}]}