Carboxyl-terminal determinants of Abelson protein important for lymphoma induction.
The carboxyl-terminal region of the Abelson protein is not absolutely required for Abelson virus transformation. However, Abelson virus strains encoding proteins missing portions of this region have a reduced ability to transform lymphoid cells in vitro and in vivo. One such strain, called P90A, is unique in that P90A-injected mice almost always develop tumors containing highly oncogenic variants that encode new forms of Abelson protein. In this work, we have examined the mechanism by which these variants are generated and used the variants to identify carboxyl-terminal protein sequences important for the induction of Abelson disease. Analysis of mice injected with helper-free P90A virus stocks demonstrates that the variants are generated during viral replication in vivo, probably as a consequence of error-prone reverse transcription. The sequence of the P90A viral genome reveals that a 19-base deletion is responsible for synthesis of the truncated Abelson protein. As a consequence of this mutation, 167 carboxyl-terminal amino acids normally found in the wild-type protein have been replaced by 33 amino acids derived from an alternative reading frame. Site-directed mutants show that the combination of the deletion and the P90A carboxyl terminus is required for the generation of variants. Thus, the particular structure of the P90A protein, not the specific residues lost or gained, alters the transforming potential of the Abelson protein. Finally, the sequence of the variants encoding smaller Abelson proteins reveals that as few as 452 v-abl-encoded amino acids are required for rapid induction of Abelson disease.
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111.
K
K
Parmar
R C
RC
Huebner
N
N
Rosenberg
D016475:3T3 Cells; D000011:Abelson murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D016679:Genome, Viral; D007942:Leukemia, Experimental / Q000382:microbiology*; D008223:Lymphoma / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D015183:Restriction Mapping; D014764:Viral Proteins / Q000235:genetics*
D009838:Oligodeoxyribonucleotides; D014764:Viral Proteins