Cooperative action of cellular proteins YB-1 and Purα with the tumor antigen of the human JC polyomavirus determines their interaction with the viral lytic control element

Nancie N. Chen, Chun Fan Chang, Gary L. Gallia, Douglas A. Kerr, Edward M. Johnson, Chavdar P. Krachmarov, Sharon M. Barr, Richard J. Frisque, Brigitte Bollag, Kamel Khalili

Research output: Contribution to journalArticle

Abstract

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 languageEnglish (US)
Pages (from-to)1087-1091
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number4
DOIs
StatePublished - Feb 14 1995
Externally publishedYes

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