QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 8, 2980-2990, August 2007

This Article Full Text Full Text (PDF) All Versions of this Article: E06-11-1054v1 18/8/2980    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ueta, R. Articles by Yamaguchi-Iwai, Y. Search for Related Content PubMed PubMed Citation Articles by Ueta, R. Articles by Yamaguchi-Iwai, Y.

Mechanism Underlying the Iron-dependent Nuclear Export of the Iron-responsive Transcription Factor Aft1p in Saccharomyces cerevisiae

Ryo Ueta^*,, Naoko Fujiwara^*, Kazuhiro Iwai^,, and Yuko Yamaguchi-Iwai^*,

*Department of Applied Molecular Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan; and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan

Submitted November 29, 2006; Revised May 15, 2007; Accepted May 18, 2007
Monitoring Editor: Karsten Weis

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.

Address correspondence to: Yuko Yamaguchi-Iwai (yukoiwai{at}kais.kyoto-u.ac.jp) or Kazuhiro Iwai (kiwai{at}med.osaka-cu.ac.jp).

Abbreviations used: AD, Gal4 transactivation domain; BD, Gal4 DNA-binding domain; CIAP, calf intestine alkaline phosphatase; DAPI, 4',6'-diamino-2-phenylindole; FOB, ferrioxamine B; GFP, green fluorescence protein; HA, hemagglutinin; NES, nuclear export signal; NLS, nuclear localization signal; TAP, tandem affinity purification.

This article has been cited by other articles:

				J. Towpik, D. Graczyk, A. Gajda, O. Lefebvre, and M. Boguta Derepression of RNA Polymerase III Transcription by Phosphorylation and Nuclear Export of Its Negative Regulator, Maf1 J. Biol. Chem., June 20, 2008; 283(25): 17168 - 17174. [Abstract] [Full Text] [PDF]

				A. Kumanovics, O. S. Chen, L. Li, D. Bagley, E. M. Adkins, H. Lin, N. N. Dingra, C. E. Outten, G. Keller, D. Winge, et al. Identification of FRA1 and FRA2 as Genes Involved in Regulating the Yeast Iron Regulon in Response to Decreased Mitochondrial Iron-Sulfur Cluster Synthesis J. Biol. Chem., April 18, 2008; 283(16): 10276 - 10286. [Abstract] [Full Text] [PDF]

				C. C. Philpott and O. Protchenko Response to Iron Deprivation in Saccharomyces cerevisiae Eukaryot. Cell, January 1, 2008; 7(1): 20 - 27. [Full Text] [PDF]