This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The goal of this project is to identify the molecular function of the poxviral virulence factor p28. P28 was shown to be an essential factor for controlling viral infection of macrophages and the inability to infect macrophages in vitro correlated with spontaneous clearance of infections in vivo. There is also some evidence that P28 protects against virally induced and UV-induced apoptosis.
Specific aim 1 of this project is to test the hypothesis that p28 protects macrophages from apoptosis. We have recently demonstrated that P28 is a RING-domain ubiquitin ligase since P28 mediates the formation of high molecular weight ubiquitinated products in the presence of ubiquitin-conjugating enzymes, ubiquitin and the ubiquitin activating enzyme E1. In addition, we observed that ubiquitin is concentrated in poxvirus factories in the presence of P28 suggesting that P28 mediates the ubiquitination of viral and/or cellular proteins in virus factories. Therefore, Specific aim 2 is to use a proteomics approach to identify potential targets that are directly or indirectly affected by P28.
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