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Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto
Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto
Electronic Thesis and Dissertation Repository
Acute myeloid leukemia (AML) is associated with mutations or chromosomal translocations in genes encoding transcription factors. PU.1 is a transcription factor that is required for the development of nearly all white blood cell types of the immune system, including B cells, granulocytes, and monocytes. Mutation of the gene encoding PU.1, SPI1 in humans and Sfpi1 in mice, is associated with AML. We hypothesized that reduced expression of PU.1 in Sfpi1BN/BNmyeloid cells will result in the development of AML in transplanted mice due to reduced repression of E2F1, leading to deregulation of the cell cycle. Results indicate that NOD/SCID/γc …
Characterizing The Contribution Of The Lxcxe Binding Cleft To Prb-Mediated Genome Stability And Tumor Suppression, Courtney H. Coschi
Characterizing The Contribution Of The Lxcxe Binding Cleft To Prb-Mediated Genome Stability And Tumor Suppression, Courtney H. Coschi
Electronic Thesis and Dissertation Repository
Condensation and segregation of mitotic chromosomes are critical processes for cellular propagation and if compromised, can lead to genomic instability. Genomic instability is known to be an active contributor to tumorigenesis, rather than being a by-product of malignant progression. The retinoblastoma protein (pRB) is the prototypic tumor suppressor. Its tumor suppressive properties are linked to its ability to negatively regulate proliferation by inhibiting E2F target gene transcription. Using a gene targeted mouse model defective for interactions mediated by the pRB LXCXE binding cleft that is distinct from E2F binding (Rb1ΔL/ΔL), I have demonstrated that LXCXE-interactions are an …