Walleye dermal sarcoma virus (WDSV) is a complex retrovirus that is etiologically associated with the induction of multifocal benign cutaneous tumors referred to as walleye dermal sarcomas. WDSV encodes three accessory proteins from open reading frames a, b, and c, that possibly direct tumor formation and, with a shift in gene expression, tumor regression.
The specific aims of this proposal seek to characterize the function of the accessory protein Orf B in order to determine its putative role in tumor formation and/or regression. Initial results show Orf B shuttles between the nucleus and cytoplasm, interacts with Receptor for Activated C Kinase 1 (RACK1), interacts with separate complexes containing PKC beta II and protein phosphatase 2A (PP2A), and protects cells from apoptosis. Immunoprecipitation experiments will be used to characterize the components of the OrfB-RACKI complex, Orf B-PKC beta II complex, and Orf B-PP2A in order to assess their function on tumor development. The mechanism(s) with which Orf B protects cells from undergoing apoptosis will be determined. Cell signaling pathway(s) responsible for protection from apoptosis will be identified by determining the specific sites of serine phosphorylation of the propapoptotic protein BAD.
| Daniels, Candelaria C; Rovnak, Joel; Quackenbush, Sandra L (2008) Walleye dermal sarcoma virus Orf B functions through receptor for activated C kinase (RACK1) and protein kinase C. Virology 375:550-60 |
