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| 說明 | 1 online resource (144 pages) |
| 文字 | text |
| 無媒介 | computer |
| 成冊 | online resource |
| 附註 | Source: Dissertations Abstracts International, Volume: 81-05, Section: B |
| Advisor: Minden, Mark David |
| Thesis (Ph.D.)--University of Toronto (Canada), 2019 |
| Includes bibliographical references |
| Acute myeloid leukemia (AML) cells with normal cytogenetics frequently harbor a TCTG insertion in exon 12 of Nucleophosmin 1 (NPM1), resulting in a frameshift creating a nuclear export signal and cytoplasmic localization of the mutant protein NPM1c. Although the mutation directs NPM1c to the cytoplasm, the underlying mechanism of how NPM1c causes AML remains incompletely understood. NPM1 participates in multiple protein-protein interactions; among those interacting proteins is the CCCTC binding factor (CTCF), the master weaver of the genome. CTCF is involved in several important nuclear functions including DNA looping, regulation of gene expression, and RNA splicing through binding to CTCF DNA binding sites. I hypothesized that NPM1c could mislocalize CTCF into the cytoplasm, thereby reducing the functional level of nuclear CTCF and so alter its regulatory roles regarding gene expression and epigenetic functions in the nucleus. Our studies verified the interaction of CTCF with NPM1. Furthermore I demonstrated that CTCF interacts with NPM1c, partially redistributing CTCF into the cytoplasm. The interaction of CTCF and NPM1c involves the amino terminus of CTCF and the last 50 amino acids on the C-terminus of NPM1. Moreover, cytoplasmic CTCF can be relocalized to the nucleus by interfering with the interaction of CTCF and NPM1c |
| Electronic reproduction. Ann Arbor, Mich. : ProQuest, 2020 |
| Mode of access: World Wide Web |
| 主題 | Oncology |
| Molecular biology |
| Biostatistics |
| Acute myeloid leukemia |
| Alternative splicing |
| CTCF |
| Cytoplasmic mislocalization |
| DNA methylation |
| NPM1c |
| Electronic books. |
| 0992 |
| 0307 |
| 0308 |
| ISBN/ISSN | 9781392551059 |
