Document Detail


FIAT control of osteoblast activity.
MedLine Citation:
PMID:  20013796     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The basic domain-leucine zipper transcription factor activating transcription factor 4 (ATF4) regulates most functions of the osteoblast. It is therefore not surprising that its activity should be regulated through several mechanisms. Factor inhibiting ATF4-mediated transcription (FIAT) is a leucine zipper nuclear molecule lacking a basic domain for DNA binding that interacts with ATF4 to repress its transcriptional activity. FIAT expression was monitored in parallel with ATF4 during osteoblastogenesis. The mechanism of ATF4 repression by FIAT was investigated through structure-function analysis. The physiological significance of FIAT expression in osteoblasts was studied through silencing FIAT in osteoblasts by RNA interference, as well as through characterization of two genetic mouse models: FIAT transgenic mice which overexpress FIAT in osteoblasts, and FIAT knockout mice. Studies to date show that FIAT and ATF4 are co-expressed in osteoblasts, and that FIAT inhibition of matrix mineralization requires dimerization with ATF4 through the second leucine zipper. Furthermore, transgenic mice overexpressing FIAT exhibit osteopenia. The phenotype of FIAT knockout mice is still under evaluation but the salient aspects are discussed here. Taken together, the results accumulated to date support the hypothesis that FIAT is a transcriptional repressor that modulates osteoblast function.
Authors:
Ren? St-Arnaud; Vice Mandic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  109     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-26     Completed Date:  2010-05-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-9     Citation Subset:  IM    
Copyright Information:
(c) 2009 Wiley-Liss, Inc.
Affiliation:
Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada H3G 1A6. rst-rnaud@shriners.mcgill.ca
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MeSH Terms
Descriptor/Qualifier:
Activating Transcription Factor 4 / genetics,  metabolism
Animals
Humans
Mice
Models, Biological
Nuclear Proteins / chemistry,  metabolism*
Osteoblasts / metabolism*
RNA, Messenger / metabolism
Grant Support
ID/Acronym/Agency:
AR53287/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/RNA, Messenger; 145891-90-3/Activating Transcription Factor 4

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


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