{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTBRG1, also known as nuclear interactor of ARF and MDM2 (NIAM), is a nuclear protein that exerts tumor suppressor–like functions by activating the p53 pathway and inhibiting cell proliferation. Early studies demonstrated that when reintroduced into cells, NIAM induces a G1 cell cycle arrest and collaborates with the ARF tumor suppressor to suppress cellular growth, even in the absence of ARF or p53. Moreover, loss of NIAM is associated with chromosomal instability and its mRNA is reduced in various human tumors, underscoring its potential role as a bona fide tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural investigations have revealed that TBRG1 contains two highly conserved motifs, FYRN and FYRC, which together form the FYR domain with a novel α + β fold. This domain architecture not only contributes to its role as a chromatin-associated protein but also underpins its interactions with key regulatory factors. In particular, TBRG1/NIAM associates with the acetyltransferase Tip60 to promote acetylation of p53 at lysine 120 and concurrently interferes with Mdm2-mediated ubiquitylation of p53. These interactions help relieve the inhibitory effects of Mdm2 on p53’s transcriptional activity, fostering an environment that supports p53-dependent growth inhibition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of B-cell lymphomas, deregulation of TBRG1/NIAM has further clinical significance. Elevated levels of miR-155 in several B-cell lymphoma subtypes have been shown to target NIAM, resulting in decreased NIAM expression and increased cellular proliferation. This finding links the oncogenic influence of miR-155 to the suppression of a key tumor inhibitory pathway, suggesting that the loss of NIAM contributes to lymphoma pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Van S Tompkins, Jussara Hagen, April A Frazier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains chromosomal stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M609612200"}], "href": "https://doi.org/10.1074/jbc.M609612200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17110379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17110379"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jussara Hagen, Van Tompkins, Amel Dudakovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Generation and characterization of monoclonal antibodies to NIAM: a nuclear interactor of ARF and Mdm2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hybridoma (Larchmt) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/hyb.2007.0533"}], "href": "https://doi.org/10.1089/hyb.2007.0533"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18582208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18582208"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "María M García-Alai, Mark D Allen, Andreas C Joerger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The structure of the FYR domain of transforming growth factor beta regulator 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.404"}], "href": "https://doi.org/10.1002/pro.404"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20506279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20506279"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sara M Reed, Jussara Hagen, Van S Tompkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.28202"}], "href": "https://doi.org/10.4161/cc.28202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24621507"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24621507"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Izabella Slezak-Prochazka, Joost Kluiver, Debora de Jong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of the miR-155 target NIAM phenocopies the growth promoting effect of miR-155 in B-cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6165"}], "href": "https://doi.org/10.18632/oncotarget.6165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26497687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26497687"}]}]}]}