Interplay between JCV Large T-antigen and Cullin-7 in Brain Cancer
| Autor: | Marsili, Stefania |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: | |
| Druh dokumentu: | Text |
| DOI: | 10.34944/dspace/1819 |
| Popis: | A convincing body of evidence suggests that ubiquitination and the ubiquitin proteasome degradation pathway play a key role in neoplastic transformation. Ubiquitination, as post-translation modification, is involved both in functional regulation and degradation of specific cellular targets known as proto-oncogenes and tumor suppressors. Oncogenic viral proteins interact both with proto-oncoproteins and tumor suppressors leading to the modulation of their cellular function by several mechanisms including ubiquitination. Interestingly, viral oncoproteins themselves can also be regulated by this post-translation modification. Additionally, viruses can assemble their own E3 ligases or regulate the activity of cellular E3 ligases. E3 ligases, involved in the final step of the ubiquitination process, are the enzymes that provide the specificity for the interaction with target substrates by the means of a large number of proteins. Recent studies on the potential correlation between viral infection and oncogenesis, have addressed the emerging role of the ubiquitination system as a possible mediator for cancer transformation. In this scenario we hypothesized that JCV T-antigen may interfere with the ubiquitination system and we investigated a possible interaction between JCV T-antigen and the E3 ligase Cul7. To prove our hypothesis we performed co-immunoprecipitation and co-immunofluorescence experiments using the glioblastoma cell lines HJC12, U87MG and HJC5. Our results indicate that JCV T-antigen and Cul7 interact in the cytoplasmic compartment. In addition, JCV T-antigen stabilizes Cul7. These observations suggest that JCV T-antigen can modulate Cul7 E3 ligase activity leading to oncogenesis. Further study addressing the biological significance of this interaction will decipher the cellular processes modulated by JCV T-antigen and Cul7 and will indicate new avenues for therapeutic intervention. Biology Ph.D. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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