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Dissertation
Identification and investigation of two novel MDM2 binding proteins: DNA polymerase epsilon and MBP-1
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
Nov 1998
DOI:
https://doi.org/10.17918/00009018
Abstract
The Mdm2 oncoprotein acts primarily by inhibiting the transcriptional activation function of the p53 tumor suppressor protein. Binding of Mdm2 to p53 is required for this effect. However, it has been shown that forms of Mdm2 exist that cannot bind to p53, but are still competent to transform cells. In addition, it has been shown that Mdm2 can bind to several other proteins including the cell cycle regulators E2F-1/DP1, pRB and p19Arf. Anteceding the identification of these binding proteins, our laboratory performed a yeast two-hybrid (Y2H) screen to identify novel Mdm2 binding proteins. A large a number of candidate interacting clones were identified. This thesis describes the development of a robust in vitro assay for testing candidate Mdm2 binding proteins and the initial characterization of two such proteins: the catalytic subunit of DNA polymerase &egr; and a novel protein MBP-1 (Mdm2 binding protein-1). Results of mapping studies for the regions of each of these proteins that are involved in these interactions are presented. We were able to confirm the interaction of the catalytic subunit of DNA polymerase &egr; with Mdm2 by co-immunoprecipitation, using both transfected cells andn from HeLa cell nuclear extract. Finally, initial attempts to examine the functional consequence(s) of the interaction between Mdm2 and the catalytic subunit of DNA polymerase &egr; are also presented.
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Details
- Title
- Identification and investigation of two novel MDM2 binding proteins
- Creators
- Nikolina Vlatkovic
- Contributors
- Mark T. Boyd (Advisor) - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- vi, 129 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Medicine (1993-1996, 1998-2002); Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021888737104721