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Identification of Additional Dimerization Partners of FIAT, the Factor Inhibiting ATF4‐Mediated Transcription
Author(s) -
STARNAUD RENÉ,
ELCHAARANI BILAL
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.028
Subject(s) - leucine zipper , atf4 , atf3 , transcription factor , microbiology and biotechnology , biology , chemistry , gene , genetics , gene expression , promoter
: FIAT is a leucine zipper protein whose name was coined for its interaction with ATF4 and the subsequent blockage of ATF4‐directed osteocalcin gene transcription. FIAT is a nuclear protein that lacks a basic DNA‐binding domain but contains three identifiable leucine zipper domains. FIAT heterodimerizes with ATF4 through one of these zippers and thereby prohibits ATF4 from binding to its cognate DNA sequence. We tested whether FIAT also interacts with additional basic domain‐leucine zipper transcriptional regulators of osteoblast activity, such as the Fos family member Fra‐1 or one of its dimerization partners, c‐Jun. Transient transfection assays in osteoblastic MC3T3‐E1 cells with the heterologous AP‐1‐tk‐luciferase reporter revealed that FIAT does not affect c‐Jun‐mediated transcription, even in the presence of the c‐Jun coactivator αNAC. However, FIAT inhibited transcriptional activation by a c‐Jun∼Fra‐1 heterodimer. Thus FIAT specifically inhibits Fra‐1 transcriptional activity. These data identify a second target of the FIAT transcriptional repressor activity and suggest that FIAT can modulate early osteoblast activity by interacting with ATF4, as well as regulate later osteoblast function through inhibition of Fra‐1.