title: Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase for mammalian thioredoxin.
abstract: Salmonella enterica encodes two virulence-related type III secretion systems in Salmonella pathogenicity islands 1 and 2, respectively. These systems mediate the translocation of protein effectors into the eukaryotic host cell, where they alter cell signaling and manipulate host cell functions. However, the precise role of most effectors remains unknown. Using a genetic screen, we identified the small, reduction/oxidation-regulatory protein thioredoxin as a mammalian binding partner of the Salmonella effector SlrP. The interaction was confirmed by affinity chromatography and coimmunoprecipitation. In vitro, SlrP was able to mediate ubiquitination of ubiquitin and thioredoxin. A Cys residue conserved in other effectors of the same family that also possess E3 ubiquitin ligase activity was essential for this catalytic function. Stable expression of SlrP in HeLa cells resulted in a significant decrease of thioredoxin activity and in an increase of cell death. The physiological significance of these results was strengthened by the finding that Salmonella was able to trigger cell death and inhibit thioredoxin activity in HeLa cells several hours post-infection. This study assigns a functional role to the Salmonella effector SlrP as a binding partner and an E3 ubiquitin ligase for mammalian thioredoxin.
authors.affiliation: Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41080 Sevilla, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Bernal-Bayard
authors.forename: Francisco
authors.initials: F
authors.lastname: Ramos-Morales
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D016923:Cell Death; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation; D011485:Protein Binding / Q000187:drug effects; D012475:Salmonella; D012480:Salmonella Infections / Q000378:metabolism / Q000473:pathology; D013879:Thioredoxins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C401846:SlrP protein, Salmonella typhimurium; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D044767:Ubiquitin-Protein Ligases
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