Document Detail


FIAT, the factor-inhibiting ATF4-mediated transcription, also represses the transcriptional activity of the bZIP factor FRA-1.
MedLine Citation:
PMID:  20392257     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
FIAT is a leucine zipper protein whose name was coined for its interaction with ATF4 and subsequent blockage of ATF4-directed osteocalcin gene transcription. FIAT lacks a basic DNA-binding domain but contains three leucine zippers; it heterodimerizes with ATF4 to prohibit binding to DNA. FIAT could also potentially interact with additional basic domain-leucine zipper transcriptional regulators of osteoblast activity, such as FRA-1. We have found that FIAT inhibits transcriptional activation by a FRA-1/c-JUN heterodimer without affecting transcription mediated by a c-JUN homodimer. The repressor effect of FIAT on FRA-1-dependent transcription was measured using reporter constructs for the natural FRA-1 targets, Mmp-9 and Mgp. The FIAT-FRA-1 interaction is mediated through the second leucine zipper of FIAT. These data confirm an additional target of the FIAT transcriptional repressor activity and suggest that FIAT can both modulate early osteoblast activity by interacting with ATF4 and regulate later osteoblast function through inhibition of FRA-1.
Authors:
René St-Arnaud; Vice Mandic; Bilal Elchaarani
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1192     ISSN:  1749-6632     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-15     Completed Date:  2010-05-05     Revised Date:  2012-10-30    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  338-43     Citation Subset:  IM    
Affiliation:
Shriners Hospital for Children, Montreal, Quebec, Canada. rst-arnaud@shriners.mcgill.ca
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MeSH Terms
Descriptor/Qualifier:
Activating Transcription Factor 4 / antagonists & inhibitors,  metabolism,  physiology
Animals
Basic-Leucine Zipper Transcription Factors / chemistry,  genetics,  metabolism,  physiology
Carrier Proteins / chemistry,  genetics,  metabolism,  physiology*
Cells, Cultured
Down-Regulation / genetics
Mice
Mutant Proteins / genetics,  metabolism,  physiology
Nuclear Proteins / chemistry,  genetics,  metabolism,  physiology*
Osteoblasts / metabolism
Protein Binding / genetics
Protein Structure, Tertiary / genetics,  physiology
Proto-Oncogene Proteins c-fos / chemistry,  genetics,  metabolism,  physiology*
Repressor Proteins / chemistry,  genetics,  metabolism,  physiology
Transcription, Genetic / genetics
Transcriptional Activation / genetics*
Transfection
Grant Support
ID/Acronym/Agency:
1R01AR053287-01A1/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Atf4 protein, mouse; 0/Basic-Leucine Zipper Transcription Factors; 0/Carrier Proteins; 0/Mutant Proteins; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Repressor Proteins; 0/Txkng protein, mouse; 0/fos-related antigen 1; 145891-90-3/Activating Transcription Factor 4

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


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