The multiple membrane-spanning segments of the BNLF-1 oncogene from Epstein-Barr virus are required for transformation.
The BNLF-1 gene from Epstein-Barr virus (EBV) induces anchorage-independent and tumorigenic growth in rodent cell lines. The BNLF-1 protein (also termed LMP) is a membrane protein, and its predicted amino acid sequence indicates that the protein has six membrane-spanning segments in addition to a short amino-terminal (approximately 25 amino acids) and a long carboxyl-terminal (approximately 200 amino acids) cytoplasmic domain. To identify the regions of the protein that are essential for its transforming activity, we have constructed deletion mutants of the BNLF-1 gene and tested them for transforming activity. Surprisingly, the entire carboxyl-terminal cytoplasmic domain is dispensable for transforming activity, whereas the putative membrane-spanning segments are essential. These observations indicate that BNLF-1 has a novel function that is distinct from the functions associated with other membrane-associated viral transforming proteins. We speculate that BNLF-1 is a receptor for a growth-promoting agent, with its trans-membrane domain involved in ligand binding, and its amino-terminal domain or cytoplasmic loops involved in coupling BNLF-1 to effector molecules in the cell, a situation analogous to the rhodopsin group of receptors.
Baichwal
V R
VR
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.
Sugden
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002458:Cell Fractionation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D015151:Immunoblotting; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D009857:Oncogenes; D010446:Peptide Fragments / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology*; D011233:Precipitin Tests; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D013539:Simian virus 40 / Q000235:genetics; D014763:Viral Matrix Proteins
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins