Human JC polyomavirus (JCV) is the etiologic agent of the neurodegenerative disease progressive multifocal leukoencephalopathy. By using JCV as a model, we investigated the role of the viral early protein tumor antigen (TAg) in the binding of two cellular proteins, Purα and YB-1, to JCV regulatory sequences. Results from band-shift assays with purified YB- 1, Purα, and TAg indicated that efficient binding of Purα, a strong activator of early gene transcription, to a single-stranded target sequence corresponding to the viral lyric control element, is diminished in the presence of the late gene activator YB-1, which recognizes the opposite strand of the Purα binding site. Of particular interest was the ability of Purα and TAg to enhance binding of YB-1 to DNA molecules without being associated with this complex. Binding studies using a mutant peptide encompassing the N terminus of YB-1 indicated that the C terminus of YB-1 is important for its DNA binding activity. The ability of Purα and TAg to increase binding of YB-1 to DNA is independent of the YB-1 C terminus. Similarly, results from band-shift assays using Purα variants indicated that two distinct regions of this protein contribute either to its ability to bind DNA or to its ability to enhance YB-1 DNA binding activity. Based on the interaction of Purα, YB-1, and TAg, and their binding to DNA, a model is proposed for the role of these proteins in transcription of viral early and late genes during the lyric cycle.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Feb 14 1995|
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