Document Detail


Two transcription activation functions in the amino terminus of the mouse estrogen receptor that are affected by the carboxy terminus.
MedLine Citation:
PMID:  9253789     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To determine the characteristics of the N-terminal transactivation domain (AF-1) of the mouse estrogen receptor (ER), we constructed a number of deletion mutants. Wild-type and mutant receptors were expressed in yeast cells and assayed for their ability to transactivate an estrogen-responsive reporter plasmid (ERE-CYCl-LacZ) that contained a single estrogen response element of the vitellogenin A2 gene promoter. Deletion of the N-terminal 121 amino acids from the mouse ER resulted in a 50% reduction in transactivation activity compared with the full-length wild-type ER. Deletion of the first 150 amino acids resulted in loss of 90% transactivation activity. An ER deletion mutant lacking residues 121-154 retained full transcriptional activity, suggesting that this region plays a significant transacting role only when the first portion is deleted. A point mutation was introduced in the C-terminal region at Met-521 in order to study the possible interaction between the C-terminal ligand-binding domain and the N-terminal AF-1 region. This mutant ER, M521G, exhibited 150% of the transcriptional activity of the wild-type ER. An M521G mutant lacking the N-terminal 121 amino acids retained full transactivation activity, whereas, M521G lacking 150 amino acids resulted in only 10% of wild-type activity. These results suggest that residues 121-154 might interact with the C terminus to affect transcription. In summary, multiple N-terminal regions in the ER were identified that function in transactivation. Furthermore, a point mutation in the C-terminal portion of the ER may change the conformation of the ER ligand-binding domain, producing a more stable receptor/ligand complex that increases transcriptional activity. These data suggest that the N- and C-terminal portions of the ER interact in a cooperative manner to activate transcription from target genes.
Authors:
O Gandini; H Kohno; S Curtis; K S Korach
Related Documents :
15652189 - Do clustered beta-propeller domains within the n-terminus of lrp1 play a functional role?
9309169 - Bleomycin hydrolase (blh1p), a multi-sited thiol protease in search of a distinct physi...
2151609 - The transmembrane anchor of the t-cell antigen receptor beta chain contains a structura...
11390119 - Cellular estrogen activity: implications for pulsed estrogen therapy.
16754659 - Stable association between g alpha(q) and phospholipase c beta 1 in living cells.
8636209 - Role of cd3 gamma in t cell receptor assembly.
18980579 - Structural analysis of a glycoside hydrolase family 43 arabinoxylan arabinofuranohydrol...
2195029 - Structure-function relationship in spinach ferredoxin-nadp+ reductase as studied by lim...
8056159 - A working hypothesis for the regulation of steroidogenesis and germ cell development in...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Steroids     Volume:  62     ISSN:  0039-128X     ISO Abbreviation:  Steroids     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-10-09     Completed Date:  1997-10-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0404536     Medline TA:  Steroids     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  508-15     Citation Subset:  IM    
Affiliation:
Receptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Genes, Reporter
Mice
Models, Biological
Mutation
Point Mutation
Receptors, Estrogen / chemistry,  genetics*,  metabolism*
Recombinant Proteins / chemistry,  genetics,  metabolism
Sequence Deletion
Transcriptional Activation*
Vitellogenins / genetics,  metabolism
Yeasts / genetics
beta-Galactosidase / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Receptors, Estrogen; 0/Recombinant Proteins; 0/Vitellogenins; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Enhanced likelihood of a golden wedding anniversary.
Next Document:  Studies directed toward a mechanistic evaluation of aromatase inhibition by androst-5-ene-7,17-dione...