The identification of human aldo-keto reductase AKR7A2 as a novel cytoglobin-binding partner.
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ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC5415844 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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The identification of human aldo-keto reductase AKR7A2 as a novel cytoglobin-binding partner.
Li Xin X Zou Shanshan S Li Zhen Z Cai Gaotai G Chen Bohong B Wang Ping P Dong Wenqi W
Cellular & molecular biology letters 20161024
Cytoglobin (CYGB), a member of the globin family, is thought to protect cells from reactive oxygen and nitrogen species and deal with hypoxic conditions and oxidative stress. However, its molecular mechanisms of action are not clearly understood. Through immunoprecipitation combined with a two-dimensional electrophoresis-mass spectrometry assay, we identified a CYGB interactor: aldo-keto reductase family 7 member A2 (AKR7A2). The interaction was further confirmed using yeast two-hybrid and co-im ...[more]
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Project description:Aldo-keto reductases (AKRs) comprise a superfamily of proteins involved in the reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least 15 AKR superfamily members have been identified so far. One of these is a newly identified gene locus, AKR1B15, which clusters on chromosome 7 with the other human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid identity to AKR1B10; AKR1B15.2 has a prolonged N terminus and consists of 344 amino acid residues. The two gene products differ in their expression level, subcellular localization, and activity. In contrast with other AKR enzymes, which are mostly cytosolic, AKR1B15.1 co-localizes with the mitochondria. Kinetic studies show that AKR1B15.1 is predominantly a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (17?-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoA conjugates and exhibits strong cofactor selectivity toward NADP(H). In accordance with its substrate spectrum, the enzyme is expressed at the highest levels in steroid-sensitive tissues, namely placenta, testis, and adipose tissue. Placental and adipose expression could be reproduced in the BeWo and SGBS cell lines, respectively. In contrast, AKR1B15.2 localizes to the cytosol and displays no enzymatic activity with the substrates tested. Collectively, these results demonstrate the existence of a novel catalytically active AKR, which is associated with mitochondria and expressed mainly in steroid-sensitive tissues.
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2007-12-30 | GSE9412 | GEO
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