ETD

Digital archive of theses discussed at the University of Pisa

 

Thesis etd-01242012-133820


Thesis type
Tesi di dottorato di ricerca
Author
ULERI, ELENA
URN
etd-01242012-133820
Thesis title
ABOLITION OF THE JC VIRUS TRANSFORMING CAPACITY BY SF2/ASF IN JCV–TRANSFORMED CELLS
Academic discipline
MED/07
Course of study
VIROLOGIA FONDAMENTALE E CLINICA
Supervisors
tutor Prof.ssa Dolei, Antonina
Keywords
  • transformation
  • SF2/ASF
  • JCV
  • tumor
Graduation session start date
02/02/2012
Availability
Full
Summary
The human neurotropic polyomavirus JC (JCV) induces a broad
range of neural–origin tumors in experimental animals and has been repeatedly detected in several human cancer, most notably neural crest– origin tumors including medulloblastomas and glioblastomas. The oncogenic activity of JCV is attributed to the viral early gene products, large T and small t antigens, as evident by results from in vitro cell culture and in vivo animal studies. The alternative splicing factor, SF2/ASF, has the capacity to exert a negative effect on transcription and splicing of JCV genes in glial cells through direct association with a specific DNA motif within the viral promoter region. In the present thesis is demonstrated that SF2/ASF suppresses large T antigen expression in JCV–transformed tumor cell lines, and the espression of SF2/ASF in such tumor cells thereby inhibits the transforming capacity of the viral tumor antigens. Moreover, down–regulation of SF2/ASF in viral–transformed tumor cell lines induces growth and proliferation of the tumor cells.
Mapping analysis of the minimal peptide domain of SF2/ASF
responsible for JCV promoter silencing and tumor suppressor activity suggests that amino acid residues 76 to 100 of SF2/ASF are functionally sufficient to suppress the growth of the tumor cells. These observations demonstrate a role for SF2/ASF in JCV–mediated cellular transformation and provide a new avenue of research to pathogenic mechanisms of JCV– induced tumors.
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