title: 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.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry and the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mahajan
authors.forename: Heidi Y
authors.initials: HY
authors.lastname: Shi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lukas
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003545:Cysteine / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D020125:Mutation, Missense; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C085344:SERPIN-B5; D015843:Serpins; D025521:Tumor Suppressor Proteins; D003545:Cysteine