Mechanisms of Regulation of Promyelocytic Leukemia (PML) Proteins by Epstein-Barr Nuclear Antigen 1 (EBNA1) and Ubiquitin Specific Protease 7 (USP7)
Year: 2013
Type: dissertation
Abstract: Promyelocytic leukemia (PML) nuclear bodies (NBs) are important nuclear structures that mediate tumour suppressive and antiviral functions. Epstein-Barr virus (EBV) has evolved mechanisms to disrupt these structures and abrogate their functions, through the EBNA1 protein. EBNA1-mediated PML NB disruption requires its interaction with two cellular proteins, CK2 and USP7, both of which negatively regulate PML in the absence of EBNA1. I determined that USP7-null cells have greatly increased PML NBs. I have demonstrated the importance of serine 393 of EBNA1, a phosphosite essential for the EBNA1-CK2 interaction. An S393A mutation abrogated the ability of EBNA1 to disrupt PML NBs, while a S393T mutation restored this ability. I have also determined that EBNA1 and USP7 can directly interact with PML proteins, primarily with PML IV. In summary, my data supports a model in which EBNA binds PML proteins directly and negatively regulates them through recruitment of CK2 and USP7.
Source: TSpace (University of Toronto)
Author: Cameron Landry
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2755130949