Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Mediates Ubiquitination-Dependent STAT3 Activation upon Salmonella enterica Serovar Typhimurium Infection

Infection and Immunity
Hai-Hua RuanJun Zhu

Abstract

Salmonella enterica serovar Typhimurium can inject effector proteins into host cells via type III secretion systems (T3SSs). These effector proteins modulate a variety of host transcriptional responses to facilitate bacterial growth and survival. Here we show that infection of host cells with S Typhimurium specifically induces the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). This TRAF6 ubiquitination is triggered by the Salmonella pathogenicity island 1 (SPI-1) T3SS effectors SopB and SopE2. We also demonstrate that TRAF6 is involved in the SopB/SopE2-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), a signaling event conducive to the intracellular growth of S Typhimurium. Specifically, TRAF6 mediates lysine-63 ubiquitination within the Src homology 2 (SH2) domain of STAT3, which is an essential step for STAT3 membrane recruitment and subsequent phosphorylation in response to S Typhimurium infection. TRAF6 ubiquitination participates in STAT3 phosphorylation rather than serving as only a hallmark of E3 ubiquitin ligase activation. Our results reveal a novel strategy in which S Typhimurium T3SS effectors broaden their functions through the activation of host p...Continue Reading

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Citations

Aug 15, 2018·Virulence·Abraham García-GilVianney Ortiz-Navarrete
Mar 30, 2018·Frontiers in Cellular and Infection Microbiology·Lidan WangShuyan Wu
Aug 14, 2019·Frontiers in Immunology·Madeleine A Wemyss, Jaclyn S Pearson
Jan 6, 2021·Veterinary Immunology and Immunopathology·Melissa S MonsonShawn M D Bearson
Mar 19, 2021·FEMS Microbiology Reviews·Amber J BartonAndrew J Pollard

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