Linked Life Data

1675637

Source:http://linkedlifedata.com/resource/pubmed/id/1675637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1991-7-24
pubmed:abstractText
Thyroid hormone receptors are cellular homologues (c-erbAs) of the v-erbA oncoprotein of the avian erythroblastosis virus. Exclusive of the viral gag region, v-erbA differs from the chick c-erbA-alpha receptor by two amino acid changes N-terminal of the DNA binding domain, two amino acid changes in the DNA binding domain, nine amino acid changes in the C-terminal region corresponding to the ligand binding domain of c-erbA, and a nine-amino acid deletion near the C terminus. v-erbA does not bind thyroid hormone and when expressed in cells inhibits the activity of wild-type thyroid hormone receptors. We reported previously that mutants of chick c-erbA/thyroid hormone receptor which lack the DNA binding domain (DBD-) inhibit transcriptional activition by wild-type thyroid hormone and retinoic acid receptors (Forman, B. M., Yang, C.-R., Au, M., Casanova, J., Ghysdael, J., and Samuels, H. H. (1989) Mol. Endocrinol. 3, 1610-1626). This dominant negative activity mapped to a series of hydrophobic heptad motifs which are conserved in the C terminus of these receptors and have been suggested to play a role in receptor dimerization. In this study we show that unlike DBD- c-erbA, DBD- v-erbA does not block receptor activity, suggesting that v-erbA acts by competing for DNA response elements rather than by formation of nonfunctional v-erbA/c-erbA heterodimers. This difference in activity was localized to a single Pro to Ser change in v-erbA just N-terminal of the last heptad motif. Introduction of this Pro to Ser change into DBD- c-erbA resulted in a protein which was inactive both functionally and in blocking receptor dimer formation in vitro.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11589-93
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:1675637-Alpharetrovirus, pubmed-meshheading:1675637-Amino Acids, pubmed-meshheading:1675637-Animals, pubmed-meshheading:1675637-Carrier Proteins, pubmed-meshheading:1675637-Chickens, pubmed-meshheading:1675637-Chimera, pubmed-meshheading:1675637-DNA, Viral, pubmed-meshheading:1675637-Gene Expression Regulation, Viral, pubmed-meshheading:1675637-Genes, Viral, pubmed-meshheading:1675637-HeLa Cells, pubmed-meshheading:1675637-Humans, pubmed-meshheading:1675637-Mutation, pubmed-meshheading:1675637-Oncogene Proteins v-erbA, pubmed-meshheading:1675637-Plasmids, pubmed-meshheading:1675637-Precipitin Tests, pubmed-meshheading:1675637-Proto-Oncogene Proteins, pubmed-meshheading:1675637-Receptors, Retinoic Acid, pubmed-meshheading:1675637-Receptors, Thyroid Hormone, pubmed-meshheading:1675637-Retroviridae Proteins, Oncogenic, pubmed-meshheading:1675637-Transcriptional Activation
pubmed:year
1991
pubmed:articleTitle
Thyroid hormone receptor/and v-erbA. A single amino acid difference in the C-terminal region influences dominant negative activity and receptor dimer formation.
pubmed:affiliation
Division of Molecular Endocrinology, New York University School of Medicine, New York 10016.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't