Abstract
A single phosphorylation event at T-antigen residue Thr124 regulates initiation of simian virus 40 DNA replication. To explore this regulatory process, a series of peptides were synthesized, centered on Thr124. These peptides contain a nuclear localization signal (NLS) and a recognition site for cyclin/Cdk kinases. When unphosphorylated, the "CDK/NLS" peptides inhibit T-antigen assembly and bind non-sequence specifically to DNA. However, these activities are greatly reduced upon phosphorylation of Thr124. Similar results were obtained by using peptides derived from the CDK/NLS region of bovine papillomavirus E1. Related studies indicate that residues in the NLS bind to DNA, whereas those in the CDK motif regulate binding. These findings are discussed in terms of the control of T-antigen double hexamer assembly and initiation of viral replication.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Amino Acid Substitution
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Antigens, Polyomavirus Transforming / chemistry*
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Antigens, Polyomavirus Transforming / genetics
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Antigens, Polyomavirus Transforming / metabolism*
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Bovine papillomavirus 1 / genetics
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Bovine papillomavirus 1 / metabolism
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Cyclin-Dependent Kinases / chemistry*
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism*
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DNA, Viral / metabolism*
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Molecular Sequence Data
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Nuclear Localization Signals / chemistry*
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Nuclear Localization Signals / genetics
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Nuclear Localization Signals / metabolism*
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Phosphorylation
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Protein Binding
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Simian virus 40 / genetics
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Simian virus 40 / metabolism
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Threonine / chemistry
Substances
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Antigens, Polyomavirus Transforming
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DNA, Viral
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Nuclear Localization Signals
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Threonine
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Cyclin-Dependent Kinases