Mechanism underlying the iron-dependent nuclear export of the iron-responsive transcription factor Aft1p in Saccharomyces cerevisiae

Aft1p is an iron-responsive transcriptional activator that plays a central role in maintaining iron homeostasis in Saccharomyces cerevisiae. Aft1p is regulated primarily by iron-induced shuttling of the protein between the nucleus and cytoplasm, but its nuclear import is not regulated by iron. Here,...

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Bibliographic Details
Published in:Molecular biology of the cell 2007-08, Vol.18 (8), p.2980-2990
Main Authors: Ueta, Ryo, Fujiwara, Naoko, Iwai, Kazuhiro, Yamaguchi-Iwai, Yuko
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - drug effects
Amino Acid Sequence
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Iron - pharmacology
Karyopherins - metabolism
Molecular Sequence Data
Mutation - genetics
Protein Binding - drug effects
Protein Structure, Tertiary
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - metabolism
Serine
Threonine
Trans-Activators - metabolism
Transcription Factors - chemistry
Transcription Factors - metabolism
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Summary:Aft1p is an iron-responsive transcriptional activator that plays a central role in maintaining iron homeostasis in Saccharomyces cerevisiae. Aft1p is regulated primarily by iron-induced shuttling of the protein between the nucleus and cytoplasm, but its nuclear import is not regulated by iron. Here, we have shown that the nuclear export of Aft1p is promoted in the presence of iron and that Msn5p is the nuclear export receptor (exportin) for Aft1p. Msn5p recognizes Aft1p in the iron-replete condition. Phosphorylation of S210 and S224 in Aft1p, which is not iron dependent, and the iron-induced intermolecular interaction of Aft1p are both essential for its recognition by Msn5p. Mutation of Cys291 of Aft1p to Phe, which causes Aft1p to be retained in the nucleus and results in constitutive activation of Aft1-target genes, disrupts the intermolecular interaction of Aft1p. Collectively, these results suggest that iron induces a conformational change in Aft1p, in which Aft1p Cys291 plays a critical role, and that, in turn, Aft1p is recognized by Msn5p and exported into the cytoplasm in an iron-dependent manner.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E06-11-1054