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Identification of a novel transcription factor impacting iron homeostasis
Author(s) -
Miller Kyle Lamar,
Theisen Christopher,
Cone Brian,
Williams John,
Logsdon Derek P,
Costa Flavia C,
White Robert A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.769.5
Subject(s) - excretion , leucine zipper , gene , transcription factor , iron homeostasis , homeostasis , atf3 , gene expression , biology , mutant , microbiology and biotechnology , endocrinology , promoter , genetics
Severe morbidity and early mortality from iron overload remains a key problem in transfusion‐dependent diseases. The goal of this study is to identify proteins partners to TTC7 which is associated with urinary iron excretion observed in mutant fsn mice in which an abnormal TTC7 protein (7 kDa larger) is produced. The fsn mouse suffers from a severe anemia accompanied by iron deficiency that results from excessive urinary iron excretion. Identification of the normal role of TTC7 protein is critical to understanding the causation of urinary iron excretion. We have identified elements of a leucine‐zipper motif in TTC7 suggesting a role in gene expression. TTC7 is localized to the nucleus of cells suggesting a role in gene regulation. We have generated CMV promoter driven FLAG‐TTC7 transgenic mice for immunoprecipation studies of FLAG‐TTC7 and its partner proteins. These precipitates are used to identify proteins involved in gene expression in association with TTC7 (identified by mass spectrophotometry). The transcriptional mechanism by which the fsn Ttc7 gene defect brings about this loss of urinary iron is expected to unveil novel therapeutic approaches for treatment of iron overload.