Tissue-specific lability and expression of avian leukosis virus long terminal repeat enhancer-binding proteins.
Avian leukosis virus (ALV) induces bursal lymphomas in chickens, after proviral integration next to the cellular myc proto-oncogene, and subsequent c-myc hyperexpression. Our previous work suggested that labile or short-lived cellular proteins interact with the viral long terminal repeat (LTR) enhancer, and binding of these proteins appeared to be essential for high rates of LTR-enhanced transcription (A. Ruddell, M. Linial, W. Schubach, and M. Groudine, J. Virol. 62:2728-2735, 1988). This lability is specific for B-lymphoid cell types, since T cells and fibroblasts show stable high rates of LTR-enhanced transcription and stable LTR-binding activity. Moreover, the lability of these proteins may be important in determining susceptibility to bursal lymphoma. In this study, we separated and characterized the labile and stable LTR-binding proteins and examined their lability and expression in different cell types. Gel shift and DNase I footprinting analyses indicated that at least five proteins interact with the 140-base-pair LTR enhancer region. These proteins were distinct by several criteria, including lability or stability after inhibition of protein synthesis, resistance to heat denaturation, chromatographic behavior, and expression in different cell types. Two binding proteins were present in many cell types and were specifically labile in B cells. A third binding protein showed hematopoietic-cell-type-specific expression and was also labile in B cells. These findings indicate that there is tissue-specific modulation of the lability and expression of ALV LTR-binding proteins, which may be important for regulation of LTR transcription enhancement and ALV bursal lymphomagenesis.
Ruddell
A
A
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Linial
M L
ML
Groudine
M
M
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D005814:Genes, Viral; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000138:chemical synthesis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012191:Retroviridae Proteins / Q000235:genetics* / Q000378:metabolism; D015678:Viral Structural Proteins / Q000235:genetics*
D004279:DNA, Viral; D015345:Oligonucleotide Probes; D012191:Retroviridae Proteins; D015678:Viral Structural Proteins; C040520:avian retrovirus proteins