Intracellular targeting of walleye dermal sarcoma virus Orf A (rv-cyclin)

Walleye dermal sarcoma virus (WDSV) induces rumors and allows or possibly d irects tumor regression. WDSV encodes a putative cyclin homologue, Orf A, a nd six variant Orf A transcripts have been identified. Northern analysis in dicated that a 3.3-kb transcript, encoding full-length Orf A, is the predom inant transcript in developing, but not regressing, tumors. Three Orf A pro teins, one full-length and two amino-truncated forms, were expressed in mam malian and piscine cells, and their intracellular locations were determined . The full-length form was nuclear and concentrated in interchromatin granu le clusters, defined by colocalization with SC-35. The amino-truncated form s were cytoplasmic. Fusion of amino-terminal portions of Orf A to a heterol ogous protein demonstrated that residues 1-112 were necessary for nuclear l ocalization. Mutation of aa K80 and/or E110 disrupted nuclear localization, suggesting a mechanism similar to that of cellular A- and D-type cyclins f or its nuclear import. (C) 2001 Academic Press.