Functional interaction between the two zinc finger domains of the v-erb A oncoprotein.
The v-erb A oncogene of avian erythroblastosis virus is a mutated and virally transduced copy of a host cell gene encoding a thyroid hormone receptor. The protein expressed by the v-erb A oncogene binds to DNA and acts as a dominant negative inhibitor of both the thyroid hormone receptor and the closely related retinoic acid receptor. The v-erb A protein has sustained two amino acid alterations within its DNA-binding domain relative to that of c-erb A, one of which, at serine 61, is known to be important for v-erb A function in the neoplastic cell. We report here that the second alteration, at threonine 78, also plays an important, although more indirect, role: alteration of the sequence at threonine 78 such that it resembles that of c-erb A can act as an intragenic suppressor and can partially restore function to a v-erb A protein rendered defective due to a mutation at position 61. Threonine 78 lies within the D-box of the v-erb A protein, a region thought to mediate receptor-receptor dimerizations, and is not in physical proximity to the serine at position 61. It therefore appears that an indirect interaction occurs between these two sites and that this interaction is crucial for v-erb A function.
Department of Microbiology, University of California, Davis 95616.
B L
BL
Hall
B G
BG
Bonde
C
C
Judelson
M L
ML
Privalsky
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis; D002467:Cell Nucleus / Q000737:chemistry; D002472:Cell Transformation, Viral / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015672:Erythroid Precursor Cells; D005347:Fibroblasts; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D018774:Oncogene Proteins v-erbA; D011487:Protein Conformation; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018774:Oncogene Proteins v-erbA; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D015682:Retroviridae Proteins, Oncogenic