DNA sequence specificity of the v-erb A oncoprotein/thyroid hormone receptor: role of the P-box and its interaction with more N-terminal determinants of DNA recognition.
The viral erb A oncogene is a mutated allele of a normal cell gene for a thyroid hormone receptor. The DNA recognition properties of the v-erb A protein are altered from those of the thyroid hormone receptor, due in part to a point mutation in the P-box of the zinc-finger domain of the viral allele. We report here the effects of systematically varying this P-box codon; our results suggest that this P-box amino acid contributes to DNA specificity not by promoting recognition of the appropriate response elements, but rather by excluding binding of the erb A protein to inappropriate half-sites. In this manner, DNA recognition by the v-erb A protein appears to differ from that by the glucocorticoid receptor. A variety of P-box amino acids were compatible with recognition of the prototypic AGGTCA half-site; intriguingly, several of these mutant erb A proteins could also recognize a variety of alternative half-site sequences. Recognition of these alternative half-sites required a compatible amino acid sequence in the N terminus of the erb A protein. Our results begin to define a code by which the identity of the amino acids in the zinc-finger and N-terminal domains is reflected in the DNA recognition properties of the receptor.
Smit-McBride
Z
Z
Section of Microbiology, University of California at Davis 95616.
Privalsky
M L
ML
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003062:Codon / Q000235:genetics; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018774:Oncogene Proteins v-erbA / Q000235:genetics*; D009857:Oncogenes; D017354:Point Mutation; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D016335:Zinc Fingers
D003062:Codon; D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D004247:DNA