title: Sulfiredoxin redox-sensitive interaction with S100A4 and non-muscle myosin IIA regulates cancer cell motility.
abstract: Sulfiredoxin (Srx) is a redox active protein that participates in the reduction of oxidized cysteine residues. Here we identify a novel function of Srx through its specific binding to S-glutathionylated S100A4 affecting its interaction with non-muscle myosin (NMIIA), thereby modulating the effect of S100A4 on NMIIA function and impacting cell adhesion and migration. Srx forms a complex with S100A4 (and has stronger affinity for S-glutathionylated S100A4), regulates its activity, and mediates redox regulation of the interaction of S100A4 with NMIIA. The consequence of this regulation is microfilament remodeling and altered cellular motility and adhesion. Srx-overexpressing cells had reduced levels of adhesion, decreased levels of Tyr(397)-phosphorylated focal adhesion kinase, and increased cell motility in wound healing assays. These results describe a novel redox-sensitive role for Srx in mediating complex protein interactions with plausible consequences for cancer cell motility.
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bowers
authors.forename: Yefim
authors.initials: Y
authors.lastname: Manevich
authors.forename: Danyelle M
authors.initials: DM
authors.lastname: Townsend
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Tew
mesh_terms: D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008958:Models, Molecular; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; C504024:SRXN1 protein, human; D024507:Nonmuscle Myosin Type IIA; D005978:Glutathione