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Tumor-suppressive maspin functions as a reactive oxygen species scavenger: importance of cysteine residues.

ABSTRACT: Maspin is a member of the serine protease inhibitor (serpin) superfamily and displays tumor-suppressing activity by controlling cell migration, proliferation, apoptosis, and adhesion. Here, we provide evidence that maspin acts as a reactive oxygen species (ROS) scavenger through oxidation of three structurally exposed cysteine thiols to sulfenic acid. Ablation of these cysteine residues in maspin resulted in a significant increase in total ROS production in mouse mammary TM40D cells. Also, cells containing a triple-cysteine mutant of maspin showed elevated ERK1/2 activity, a downstream target of ROS, and enhanced proliferation and colony formation. These findings establish a novel mechanism by which maspin utilizes its cysteine thiols to inhibit oxidative stress and cell growth.

SUBMITTER: Mahajan N

PROVIDER: S-EPMC3630891 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Tumor-suppressive maspin functions as a reactive oxygen species scavenger: importance of cysteine residues.

Mahajan Nitin N Shi Heidi Y HY Lukas Thomas J TJ Zhang Ming M

The Journal of biological chemistry 20130307 16

Maspin is a member of the serine protease inhibitor (serpin) superfamily and displays tumor-suppressing activity by controlling cell migration, proliferation, apoptosis, and adhesion. Here, we provide evidence that maspin acts as a reactive oxygen species (ROS) scavenger through oxidation of three structurally exposed cysteine thiols to sulfenic acid. Ablation of these cysteine residues in maspin resulted in a significant increase in total ROS production in mouse mammary TM40D cells. Also, cells ...[more]

PMID: 23471964

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