Intracellular targeting of walleye dermal sarcoma virus Orf A (rv-cyclin).
Walleye dermal sarcoma virus (WDSV) induces tumors and allows or possibly directs tumor regression. WDSV encodes a putative cyclin homologue, Orf A, and six variant Orf A transcripts have been identified. Northern analysis indicated that a 3.3-kb transcript, encoding full-length Orf A, is the predominant transcript in developing, but not regressing, tumors. Three Orf A proteins, one full-length and two amino-truncated forms, were expressed in mammalian and piscine cells, and their intracellular locations were determined. The full-length form was nuclear and concentrated in interchromatin granule clusters, defined by colocalization with SC-35. The amino-truncated forms were cytoplasmic. Fusion of amino-terminal portions of Orf A to a heterologous protein demonstrated that residues 1-112 were necessary for nuclear localization. Mutation of aa K80 and/or E110 disrupted nuclear localization, suggesting a mechanism similar to that of cellular A- and D-type cyclins for its nuclear import.
Rovnak
J
J
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.
Casey
J W
JW
Quackenbush
S L
SL
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D016366:Open Reading Frames; D012367:RNA, Viral; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins; D012509:Sarcoma / Q000473:pathology / Q000821:virology; D000068103:Serine-Arginine Splicing Factors; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D002843:Chromatin; D016213:Cyclins; D009687:Nuclear Proteins; D012367:RNA, Viral; D012191:Retroviridae Proteins; D012261:Ribonucleoproteins; D014764:Viral Proteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors