Wendzicki, Justin
(2020)
Comparative analyses of tumorigenic mechanisms of Merkel cell polyomavirus T antigens.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The work described in this dissertation began in 2013 and is focused on characterizing the mechanisms by which Merkel cell polyomavirus (MCV) Large T (LT) and small T (sT) antigens induce tumorigenesis through comparative analyses with oncoproteins from other tumor viruses. A peptide motif in the C-terminal region of MCV LT that bears little sequence homology with other human polyomavirus LT proteins is shown to be critical for maintaining stability of the full-length LT protein (Chapter 3). Comparison between LT antigens of MCV and SV40 demonstrate that MCV LT in direct contrast to SV40 LT is incapable of avidly binding tumor suppressor p53 and inhibiting its transactivation capabilities (Chapter 4). Lastly, promiscuous E3 ligase targeting by MCV sT through its LT-stabilization domain (LSD) results in the formation of a genomically unstable phenotype, a known hallmark of cancer (Chapter 5). Many of the features of genomic instability induced by MCV sT such as centrosome overduplication parallel what has been observed previously for human papillomavirus 16 E7 oncoprotein. Overall, these comparative analyses have not only provided greater insight into MCV biology and how its T antigens function in causing an aggressive cancer like Merkel cell carcinoma (MCC), but they have also revealed new avenues for continued study involving MCV T antigens that will continue to move the field of tumor virology forward.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
10 January 2020 |
| Date Type: |
Publication |
| Defense Date: |
6 December 2019 |
| Approval Date: |
10 January 2020 |
| Submission Date: |
17 December 2019 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
180 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Virology and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Merkel cell polyomavirus, Merkel cell carcinoma, tumorigenesis, T antigens |
| Date Deposited: |
10 Jan 2020 19:29 |
| Last Modified: |
10 Jan 2020 19:29 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38052 |
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