a1/EBP: a leucine zipper protein that binds CCAAT/enhancer elements in the avian leukosis virus long terminal repeat enhancer.
Avian leukosis virus (ALV) induces bursal lymphoma in chickens after integration of proviral long terminal repeat (LTR) enhancer sequences next to the c-myc proto-oncogene. Labile LTR-binding proteins appear to be essential for c-myc hyperexpression, since both LTR-enhanced transcription and the activities of LTR-binding proteins are specifically decreased after inhibition of protein synthesis (A. Ruddell, M. Linial, W. Schubach, and M. Groudine, J. Virol. 62:2728-2735, 1988). This lability is restricted to hematopoietic cells from ALV-susceptible chicken strains, suggesting that the labile proteins play an important role in lymphomagenesis. The major labile activity binding to the a1 LTR region (A. Ruddell, M. Linial, and M. Groudine, Mol. Cell. Biol. 12:5660-5668, 1989) was purified from bursal lymphoma cells by conventional and oligonucleotide affinity chromatography, yielding three proteins of 35, 40, and 42 kDa. More than one of these species binds the a1 LTR region, as judged by gel shift analysis. A gene encoding an a1-binding protein (designated a1/EBP) was cloned by screening a bursal lymphoma cDNA library for fusion proteins binding the a1 LTR site. DNase I footprinting and gel shift assays indicate that the a1/EBP fusion protein binds multiple LTR CCAAT/enhancer elements in a pattern similar to that of the purified B-cell protein. DNA sequence analysis shows that this 2.2-kb cDNA encodes a 209-amino-acid open reading frame containing carboxy-terminal basic and leucine zipper motifs, indicating that a1/EBP encodes a novel member of the leucine zipper family of transcription factors.
Bowers
W J
WJ
Department of Microbiology and Immunology, University of Rochester Medical Center, New York 14642.
Ruddell
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D030161:Avian Proteins; D001483:Base Sequence; D002060:Bursa of Fabricius / Q000166:cytology; D022762:CCAAT-Enhancer-Binding Proteins; D003001:Cloning, Molecular; D004277:DNA, Single-Stranded; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005796:Genes / Q000235:genetics; D016350:Leucine Zippers; D008223:Lymphoma / Q000737:chemistry / Q000662:veterinary; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification
D030161:Avian Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D004277:DNA, Single-Stranded; D014157:Transcription Factors