The CREB, ATF-1, and ATF-2 transcription factors from bovine leukemia virus-infected B lymphocytes activate viral expression.
Efficient transcription and replication of the bovine leukemia virus (BLV) genome require both the viral long terminal repeat (LTR) and the virus-coded transcriptional activator Tax, which functions through a 21-bp sequence (Tax-responsive element [TxRE]) which is repeated three times within the LTR. Since Tax does not bind directly to DNA, host cell transcription factors play a central role in BLV expression. Electrophoretic mobility shift assays with nuclear extracts prepared with infected bovine B lymphocytes revealed five TxRE-specific complexes (C1, C2, C3, C4, and C5). Here, by using a UV-induced indirect labeling technique (UV cross-linking) in conjunction with mobility shift assays, eight major polypeptides of 31, 33, 42, 46, 51, 57, 87, and 119 kDa were identified within these five complexes. Immunoprecipitation experiments identified the 57- and 119-kDa proteins as cyclic AMP response element-binding (CREB) proteins, the 46- and 51-kDa proteins as activating transcription factor-1 (ATF-1), and the 87-kDa as protein ATF-2. All of these proteins (except the ATF-1 protein of 51 kDa) belong to the complex C1, which is the major complex identified in freshly isolated BLV-infected lymphocytes from cattle with persistent lymphocytosis. In transient-cotransfection experiments, these three transcription factors were able to activate LTR-directed gene expression in the presence of protein kinase A or Ca2+/calmodulin-dependent protein kinase IV. CREB protein, ATF-1, and ATF-2 thus appear to be the major transcription factors involved in the early stages of viral expression.
Adam
E
E
Department of Molecular Biology, University of Brussels, Belgium.
Kerkhofs
P
P
Mammerickx
M
M
Burny
A
A
Kettmann
R
R
Willems
L
L
D051697:Activating Transcription Factor 1; D051698:Activating Transcription Factor 2; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000821:virology*; D001483:Base Sequence; D002417:Cattle; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D001909:Leukemia Virus, Bovine / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014775:Virus Activation
D051697:Activating Transcription Factor 1; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D014157:Transcription Factors