{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMTBP is a multifunctional protein that plays critical roles in cell cycle regulation and DNA replication. Initially identified as an MDM2-binding partner, MTBP can induce G₁ arrest, an effect that is overcome by MDM2, thereby contributing to the regulation of p53 levels and activity through promoting MDM2-mediated ubiquitination and stabilization. In addition, MTBP interacts with the replication factor Treslin/TICRR to facilitate the assembly of the activated CMG helicase during origin firing, integrating signals from cyclin-dependent kinases and the DNA damage response pathways. Genome-wide mapping further reveals that MTBP is broadly associated with transcriptional‐regulatory elements in open chromatin, suggesting its role in marking replication initiation sites."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDuring mitosis, MTBP contributes to ensuring proper chromosome segregation by localizing to kinetochores. It is involved in recruiting or retaining the Mad1/Mad2 complex during prometaphase, thereby maintaining an effective spindle assembly checkpoint. Subsequent proteolytic degradation of MTBP appears necessary for silencing the checkpoint as cells progress from metaphase to anaphase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, MTBP exhibits dual and context-dependent functions. On one hand, MTBP suppresses metastasis through its interaction with alpha-actinin-4 (ACTN4), inhibiting cellular migration and filopodia formation in various cancer models including osteosarcoma and hepatocellular carcinoma, with reduced MTBP expression correlating with increased metastatic potential. On the other hand, MTBP can act as an oncogenic cofactor by associating with MYC and its cofactors TIP48/TIP49, thereby enhancing MYC-driven transcription, proliferation, and neoplastic transformation. In triple-negative breast cancer cells, MTBP is frequently overexpressed and required for cell survival and anchorage-independent growth, underscoring its potential as a therapeutic target. Moreover, studies in hepatocellular carcinoma further suggest that MTBP expression is frequently attenuated in tumors, linking its loss to enhanced invasive behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M T Boyd, N Vlatkovic, D S Haines "}, {"type": "b", "children": [{"type": "t", "text": "A novel cellular protein (MTBP) binds to MDM2 and induces a G1 arrest that is suppressed by MDM2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M004252200"}], "href": "https://doi.org/10.1074/jbc.M004252200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10906133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10906133"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dominik Boos, Mona Yekezare, John F X Diffley "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a heteromeric complex that promotes DNA replication origin firing in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1237448"}], "href": "https://doi.org/10.1126/science.1237448"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23704573"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23704573"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mark Brady, Nikolina Vlatkovic, Mark T Boyd "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of p53 and MDM2 activity by MTBP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.2.545-553.2005"}], "href": "https://doi.org/10.1128/MCB.25.2.545-553.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15632057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15632057"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Akiko Kumagai, William G Dunphy "}, {"type": "b", "children": [{"type": "t", "text": "Binding of the Treslin-MTBP Complex to Specific Regions of the Human Genome Promotes the Initiation of DNA Replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2020.108178"}], "href": "https://doi.org/10.1016/j.celrep.2020.108178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32966791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32966791"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "N Agarwal, Y Tochigi, A S Adhikari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MTBP plays a crucial role in mitotic progression and chromosome segregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2010.189"}], "href": "https://doi.org/10.1038/cdd.2010.189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21274008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21274008"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "N Agarwal, A S Adhikari, S V Iyer, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MTBP Promotes the Invasion and Metastasis of Hepatocellular Carcinoma by Enhancing the MDM2-Mediated Degradation of E-Cadherin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dig Dis Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10620-015-3824-4"}], "href": "https://doi.org/10.1007/s10620-015-3824-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26280083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26280083"}]}]}]}