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J. Biol. Chem., Vol. 275, Issue 21, 16227-16234, May 26, 2000
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From the Department of Microbiology and Immunology, University of
Illinois at Chicago, Chicago, Illinois 60612
Iron regulatory proteins (IRP) are
sequence-specific RNA-binding proteins that mediate iron-responsive
gene regulation in animals. IRP1 is also the cytosolic isoform of
aconitase (c-aconitase). This latter activity could complement a
mitochondrial aconitase mutation (aco1) in
Saccharomyces cerevisiae to restore glutamate prototrophy.
In yeast, the c-aconitase activity of IRP1 was responsive to iron
availability in the growth medium. Although IRP1 expression rescued
aco1 yeast from glutamate auxotrophy, cells remained
growth-limited by glutamate, displaying a slow-growth phenotype on
glutamate-free media. Second site mutations conferring
enhanced cytosolic
aconitase-dependent (ECA) growth were
recovered. Relative c-aconitase activity was increased in extracts of
strains harboring these mutations. One of the ECA mutations was found
to be in the gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase
(IDP2). This mutation, an insertion of a Ty delta element
into the 5' region of IDP2, markedly elevates expression of
Idp2p in glucose media. Our results demonstrate the physiological
significance of the aconitase activity of IRP1 and provide insight into
the role of c-aconitase with respect to iron and cytoplasmic redox regulation.
The Aconitase Function of Iron Regulatory Protein 1
GENETIC STUDIES IN YEAST IMPLICATE ITS ROLE IN IRON-MEDIATED
REDOX REGULATION*
,
*
This work was supported by Grant DK47281 from the National
Institutes of Health (to W. E. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Dept. of Microbiology and Immunology, Indiana
University School of Medicine and Walther Cancer Institute, Indianapolis, IN 46202-5120.
§
To whom correspondence should be addressed: Dept. of Microbiology
and Immunology, m/c 790, University of Illinois at Chicago, 835 S. Wolcott, Chicago, IL 60612. Tel.: 312-996-8576; Fax: 312-996-6415; E-mail: wwalden@uic.edu.
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