Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Activating Transcription Factor 4 / antagonists & inhibitors
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Activating Transcription Factor 4 / metabolism
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Activating Transcription Factor 4 / physiology
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Animals
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Basic-Leucine Zipper Transcription Factors / chemistry
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / metabolism
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Basic-Leucine Zipper Transcription Factors / physiology
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cells, Cultured
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Co-Repressor Proteins
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Down-Regulation / genetics
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Mice
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Mutant Proteins / genetics
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Mutant Proteins / metabolism
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Mutant Proteins / physiology
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Osteoblasts / metabolism
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Protein Binding / genetics
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Protein Structure, Tertiary / genetics
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Protein Structure, Tertiary / physiology
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Proto-Oncogene Proteins c-fos / chemistry
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism
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Proto-Oncogene Proteins c-fos / physiology*
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Repressor Proteins / physiology
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Transcription, Genetic / genetics
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Transcriptional Activation / genetics*
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Transfection
Substances
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Atf4 protein, mouse
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Basic-Leucine Zipper Transcription Factors
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Carrier Proteins
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Co-Repressor Proteins
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Mutant Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins c-fos
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Repressor Proteins
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Txlng protein, mouse
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fos-related antigen 1
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Activating Transcription Factor 4