{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe study by"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "focused on canonical and noncanonical Wnt signaling in B lymphocytes—detailing how Wnt3a and associated molecules such as GCKR regulate beta‐catenin stabilization and JNK activation. Although this work did not directly address miR4749, it sets an important cellular context by delineating complex signaling cascades where other microRNAs might exert regulatory roles.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInvestigations probing the tumor suppressor p53 have shown that miR4749 directly interacts with the p53 DNA-binding domain. Specifically, the microRNA binds near the L3 loop and H1 helix adjacent to the Zn‐finger motif, mimicking the structure of p53’s DNA response element. This binding is characterized by a moderate to high affinity and suggests that miR4749 may competitively inhibit p53’s association with its target DNA, potentially impairing p53-dependent transcription and related tumor suppressor functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary research has further revealed that miR4749 forms a stable complex with Human Serum Albumin (HSA) through interactions with a positively charged pocket on the protein. Using fluorescence spectroscopy and computational docking, it was demonstrated that HSA can bind miR4749 with appreciable affinity, implying a role for HSA as a natural carrier that may protect and facilitate the targeted delivery of miR4749 under physiological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chong-Shan Shi, Ning-Na Huang, Kathleen Harrison, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mitogen-activated protein kinase kinase kinase kinase GCKR positively regulates canonical and noncanonical Wnt signaling in B lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00209-06"}], "href": "https://doi.org/10.1128/MCB.00209-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16914735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16914735"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anna Rita Bizzarri, Salvatore Cannistraro "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of a Direct Interaction between miR4749 and the Tumor Suppressor p53 by Fluorescence, FRET and Molecular Modeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom10020346"}], "href": "https://doi.org/10.3390/biom10020346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32098369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32098369"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valentina Botti, Silvia Marrone, Salvatore Cannistraro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction between miR4749 and Human Serum Albumin as Revealed by Fluorescence, FRET, Atomic Force Spectroscopy and Computational Modelling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23031291"}], "href": "https://doi.org/10.3390/ijms23031291"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35163220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35163220"}]}]}]}