Genetic dissection of functional domains within the avian erythroblastosis virus v-erbA oncogene.
The avian erythroblastosis virus v-erbA locus potentiates the oncogenic transformation of erythroid and fibroblast cells and is derived from a host cell gene encoding a thyroid hormone receptor. We report here the use of site-directed mutagenesis to identify and characterize functional domains within the v-erbA protein. Genetic lesions introduced into a putative hinge region or at the extreme C-terminus of the v-erbA coding domain had no significant effect on the biological activity of this polypeptide. In contrast, mutations introduced within the cysteine-lysine-arginine-rich center of the v-erbA coding region, a DNA-binding domain in the thyroid and steroid hormone receptors, abolished or severely compromised the ability of the viral protein to function. Our results suggest that the mechanism of action of the v-erbA protein in establishing the neoplastic phenotype is closely related to its ability to interact with DNA, presumably thereby altering expression of host target genes by either mimicking or interfering with the action of the normal c-erbA gene product.
Privalsky
M L
ML
Department of Microbiology, University of California, Davis 95616.
Boucher
P
P
Koning
A
A
Judelson
C
C
D001355:Alpharetrovirus / Q000235:genetics*; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001853:Bone Marrow; D002453:Cell Cycle; D002472:Cell Transformation, Viral; D002645:Chickens; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003673:Defective Viruses / Q000235:genetics; D005347:Fibroblasts; D005786:Gene Expression Regulation; D004915:Leukemia, Erythroblastic, Acute / Q000382:microbiology; D008667:Metalloproteins / Q000235:genetics*; D009857:Oncogenes; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014760:Viral Fusion Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; D008667:Metalloproteins; D014157:Transcription Factors; D014760:Viral Fusion Proteins