The Herpesvirus Saimiri Open Reading Frame 73 Gene Product Interacts with the Cellular Protein p32

AUTOR(ES)

Hall, Kersten T.

FONTE

American Society for Microbiology

RESUMO

The role of the gamma-2 herpesvirus open reading frame (ORF) 73 gene product has become the focus of considerable interest. It has recently been shown that the Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is expressed during a latent infection and can modulate both viral and cellular gene expression. The herpesvirus saimiri (HVS) ORF 73 gene product has some sequence homology to LANA; however, the role of HVS ORF 73 is unknown. We have previously demonstrated that HVS ORF73 is expressed in a stably transduced human carcinoma cell line, where HVS genomes persist as nonintegrated circular episomes. This implies that there may be some functional homology between these proteins. To further investigate the role of the HVS ORF 73 protein, the yeast two-hybrid system was employed to identify interacting cellular proteins. We demonstrate that ORF 73 interacts with the cellular protein p32 and triggers the accumulation of p32 in the nucleus. Using reporter gene-based transient-transfection assays, we demonstrate that ORF 73 can transactivate a number of heterologous promoter constructs and also upregulate its own promoter. Moreover, ORF 73 and p32 act synergistically to transactivate these promoters. The binding of ORF 73 to p32 is mediated by an amino-terminal arginine-rich domain, which contains two functionally distinct nuclear localization signals. The p32 binding domains are required for ORF 73 transactivating abilities and for ORF 73 to induce nuclear accumulation of p32. These results suggest that ORF 73 can function as a regulator of gene expression and that p32 is involved in ORF 73-dependent transcriptional activation.

Documentos Relacionados

• The Open Reading Frame (ORF) 50a Gene Product Regulates ORF 57 Gene Expression in Herpesvirus Saimiri
• The Immediate-Early Gene Product Encoded by Open Reading Frame 57 of Herpesvirus Saimiri Modulates Gene Expression at a Posttranscriptional Level
• The Open Reading Frame 57 Gene Product of Herpesvirus Saimiri Shuttles between the Nucleus and Cytoplasm and Is Involved in Viral RNA Nuclear Export
• Deletion mutants of herpesvirus saimiri define an open reading frame necessary for transformation.
• Herpesvirus Saimiri Open Reading Frame 50 (Rta) Protein Reactivates the Lytic Replication Cycle in a Persistently Infected A549 Cell Line