Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 819-828 |
| Number of pages | 10 |
| Journal | Molecular Endocrinology |
| Volume | 8 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1994 |
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ASJC Scopus subject areas
- Molecular Biology
- Endocrinology, Diabetes and Metabolism
Cite this
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. / McBride, Zeljka; Privalsky, Martin L.
In: Molecular Endocrinology, Vol. 8, No. 7, 07.1994, p. 819-828.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - DNA sequence specificity of the v-erb A oncoprotein/thyroid hormone receptor
T2 - Role of the P-box and its interaction with more N-terminal determinants of DNA recognition
AU - McBride, Zeljka
AU - Privalsky, Martin L.
PY - 1994/7
Y1 - 1994/7
N2 - 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.
AB - 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.
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U2 - 10.1210/me.8.7.819
DO - 10.1210/me.8.7.819
M3 - Article
C2 - 7984144
AN - SCOPUS:0028290465
VL - 8
SP - 819
EP - 828
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 7
ER -