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Full-Text Articles in Life Sciences
Post-Translational Control Of Retinoblastoma Protein Phosphorylation, Paul M. Stafford
Post-Translational Control Of Retinoblastoma Protein Phosphorylation, Paul M. Stafford
Electronic Thesis and Dissertation Repository
The retinoblastoma tumor suppressor protein (pRB) functions through multiple mechanisms to serve as a tumor suppressor. pRB has been well characterized to be inactivated through phosphorylation by CDKs. pRB dephosphorylation and activation is a much less characterized aspect of pRB function. In this thesis, I detail work to study the post translational control of pRB phosphorylation. Here I present work detailing efforts to generate a gene targeted mouse which disrupts PP1 binding to the C-terminus of pRB, allowing for detailed study of the mechanisms of pRB dephosphorylation. This work also details an examination of acetylation in the C-terminus of pRB, …
Investigating The Role Of Retinoblastoma Protein And Transforming Growth Factor-Beta In Growth Inhibition, Mehdi Amiri
Investigating The Role Of Retinoblastoma Protein And Transforming Growth Factor-Beta In Growth Inhibition, Mehdi Amiri
Electronic Thesis and Dissertation Repository
The Retinoblastoma protein (pRB) is a key regulator of cell proliferation in the G1 phase of the cell cycle. The LxCxE binding cleft is a highly conserved region of pRB. Using a knock-in mouse model, called Rb1∆L, with disrupted pRB and LxCxE interactions, our lab has shown that epithelial cells from Rb1∆L/∆L mice do not respond to TGF-β1 mediated growth arrest. Using shRNAs to deplete the expression of components of LxCxE motif containing complexes, data showed that SAP18 is not involved in TGF-β1 mediated growth arrest. However, depletion of SAP30 and MTA2 compromised TGF-β1 mediated growth arrest. …
Characterizing The Role Of The Retinoblastoma Protein Lxcxe Binding Cleft In Cellular Senescence And Tumor Suppression, Srikanth Talluri
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 …
Dissecting The Molecular Role Of Distinct Binding Interfaces On The Retinoblastoma Tumor Suppressor In Growth Control And Tumorigenesis., Matthew J. Cecchini
Dissecting The Molecular Role Of Distinct Binding Interfaces On The Retinoblastoma Tumor Suppressor In Growth Control And Tumorigenesis., Matthew J. Cecchini
Electronic Thesis and Dissertation Repository
The retinoblastoma tumor suppressor protein (pRB) functions to maintain proliferative control and act as a barrier to tumorigenesis. pRB is capable of regulating E2F transcription factors to mediate control of proliferation through transcriptional regulation of S-phase target gene expression. In addition, pRB can stabilize the CDK inhibitor p27 through an interaction with two ubiquitin ligase complexes. Further, pRB is capable of forming a unique interaction with E2F1 termed the ‘specific’ interaction that is capable of blocking E2F1 induced apoptosis. These functions of pRB are mediated by distinct binding interfaces and their contributions to the overall functionality of pRB are not …