Ontogeny of the v-erbA oncoprotein from the thyroid hormone receptor: an alteration in the DNA binding domain plays a role crucial for v-erbA function.
The avian erythroblastosis virus v-erbA oncogene is imprecisely derived from a cellular gene (c-erbA) encoding a thyroid hormone receptor: the v-erbA protein has sustained both small terminal deletions and internal amino acid sequence changes relative to c-erbA. We report here that one of these missense differences between v- and c-erbA proteins, located in a zinc finger DNA binding domain, has dramatic effects on the biological activities of the encoded protein. Back mutation of the viral coding sequence to resemble c-erbA at this site severely impairs erythroid transformation and produces subtle changes in DNA binding by the encoded protein, suggesting that differences in DNA binding by the viral and cellular proteins may be involved in the activation of v-erbA as an oncogene.
Bonde
B G
BG
Department of Microbiology, University of California, Davis 95616.
Sharif
M
M
Privalsky
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D001353:Avian Leukosis / Q000473:pathology; D001354:Avian Leukosis Virus / Q000235:genetics*; D001483:Base Sequence; D002472:Cell Transformation, Viral; D002645:Chickens; D004279:DNA, Viral / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000382:microbiology; D008969:Molecular Sequence Data; D009154:Mutation; D018774:Oncogene Proteins v-erbA; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics*; D009857:Oncogenes; D011487:Protein Conformation; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics
D004279:DNA, Viral; D018774:Oncogene Proteins v-erbA; D009856:Oncogene Proteins, Viral; D011988:Receptors, Thyroid Hormone; D015682:Retroviridae Proteins, Oncogenic