Functional organization of the Bel-1 trans activator of human foamy virus.
Human foamy virus encodes a 300-amino-acid nuclear regulatory protein termed Bel-1 that is required for human foamy virus replication in culture. Bel-1 is a potent trans-activator of gene expression directed by the homologous HFV long terminal repeat as well as the long terminal repeat of human immunodeficiency virus type 1. We have used mutational analysis to define several discrete functional domains within Bel-1. The C-terminal approximately 50 amino acids of Bel-1 are shown to be essential for Bel-1 activity but can be effectively substituted by the C-terminal activation domain of VP16. We therefore conclude that the Bel-1 C terminus forms part of an activation domain. Mutations within a central, approximately 100-amino-acid segment of Bel-1 preclude trans-activation by either Bel-1 or the Bel-1/VP16 chimera. These sequences are therefore proposed to direct the interaction of Bel-1 with its viral DNA target sequences. A short Bel-1 segment located between the activation and binding domains is shown to mediate the nuclear localization of this regulatory protein. Although the functional organization of Bel-1 therefore appears comparable to that reported for other eukaryotic transcriptional activators, Bel-1 does not contain sequences homologous to known transcriptional activation or DNA-binding motifs.
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
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D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012191:Retroviridae Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion; D016092:Spumavirus / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012191:Retroviridae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C074061:bel1 protein, Human foamy virus; C080099:bet protein, human foamy virus