Biochemistry, Biophysics, and Structural Biology Commons^™

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 (Rb1^ΔL/ΔL), I have demonstrated that LXCXE-interactions are an …