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Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Western University

2013

LXCXE

Articles 1 - 2 of 2

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Characterizing The Role Of The Retinoblastoma Protein Lxcxe Binding Cleft In Cellular Senescence And Tumor Suppression, Srikanth Talluri Jul 2013

Characterizing The Role Of The Retinoblastoma Protein Lxcxe Binding Cleft In Cellular Senescence And Tumor Suppression, Srikanth Talluri

Electronic Thesis and Dissertation Repository

The Retinoblastoma protein (pRB) is a key regulator of the cell cycle and is functionally inactivated in most cancers. pRB has been proposed to utilize simultaneous interactions with E2F transcription factors and chromatin regulatory proteins to repress transcription and block cell cycle progression. The goal of this study is to characterize the physiological role of pRB interactions with chromatin regulatory proteins. I used gene targeted mice carrying point mutations in the murine Rb1 gene (Rb1∆L) that specifically disrupt pRB’s LXCXE binding cleft, and thereby its ability to interact with chromatin regulatory proteins while leaving its ability to …


Characterizing The Contribution Of The Lxcxe Binding Cleft To Prb-Mediated Genome Stability And Tumor Suppression, Courtney H. Coschi Apr 2013

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 …