- Collection:
- Atlanta University and Clark Atlanta University Theses and Dissertations
- Title:
- Effects of bpv e5 on tel-pdgfbr and the jak-stat pathway, 2005
- Creator:
- Louden, Erica D.
- Date of Original:
- 2005-05-01
- Subject:
- Degrees, Academic
Dissertations, Academic - Location:
- United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
- Medium:
- theses
dissertations - Type:
- Text
- Format:
- application/pdf
- Description:
- An altered Platelet Derived Growth Factor Beta receptor (PDGFPr) gene containing a fused transcription factor, Transcription ETS Leukemia (TEL), creates the protein TEL-PDGFpr found in Chronic Myelomonocytic Leukemia (CMML). PDGFPr is a well-characterized plasma membrane receptor with endogenous tyrosine kinase activity. The E5 protein of bovine papillomavirus (BPV E5) binds and activates PDGFPr, activating JAK-STAT pathways which alter gene regulation for growth and differentiation. This study examines alterations in JAK-STAT pathways and cellular growth modifications induced by BPV E5. Viral infection of BaF3 TEL-PDGFPr murine hematopoietic cells with BPV E5, produced BaF3 TEL-PDGFPr/BPV E5 (BaF3 TP/E5). Immunoprecipitation Western blot analysis of cytoplasmic, membrane and nuclear fractions revealed that TEL-PDGFpr and BPV E5 colocalize in the cytoplasm. Coimmunoprecipitation of BPV E5 with TEL-PDGFPr suggests the proteins are associated. BPV E5 association with TEL-PDGFpr induces expression of TYK 2. This appears to correlate with a 3-fold decrease in anchorage independent growth phenotype as shown by soft agar assay. STAT 5a/b expression and phosphorylation was induced by BPV E5 and cell growth increased as measured by the MTT assay. Protein extracts from BAF3 TP/E5 bind STATs 1, 3, and 5 to GAS/ISRE DNA sequences in Electrophoretic Mobility Shift Assays. This suggests that STATs 1, 3, and 5 bind to DNA and may participate in transcriptional events related to growth of these cells. This study demonstrates that BPV E5 interacts with TEL-PDGFPr and that BPV E5 introduction into the cell line correlates negatively with anchorage independent growth, while growth rate increases. Possible mechanisms for these phenomena could be induction of STAT 5a/b expression and phosphorylation. Understanding JAK-STAT pathway molecules modified by BPV E5, information may be yielded about proteins responsible for transformation and growth changes. Manipulation of TEL-PDGFPr activation by BPV E5 could lead to therapeutic targets for growth of leukemia cells and CMML patients.
Date of award: 2005-05-01
Degree type: dissertation
Degree name: Doctor of Philosophy (PhD)
Granting institution: Clark Atlanta University
Department: Department of Biological Sciences
Advisor: Kegler-Ebo, Deena M. - Metadata URL:
- http://hdl.handle.net/20.500.12322/cau.td:2005_louden_erica_d
- Holding Institution:
- Atlanta University Center Robert W. Woodruff Library
- Rights:
-
