SseK3 Is a Salmonella Effector That Binds TRIM32 and Modulates the Host's NF-kappa B Signalling Activity

Download
Author
Yang, Z; Soderholm, A; Lung, TWF; Giogha, C; Hill, MM; Brown, NF; Hartland, E; Teasdale, RDDate
2015-09-22Source Title
PLoS OnePublisher
PUBLIC LIBRARY SCIENCEAffiliation
Microbiology and ImmunologyUniversity General
Metadata
Show full item recordDocument Type
Journal ArticleCitations
Yang, Z., Soderholm, A., Lung, T. W. F., Giogha, C., Hill, M. M., Brown, N. F., Hartland, E. & Teasdale, R. D. (2015). SseK3 Is a Salmonella Effector That Binds TRIM32 and Modulates the Host's NF-kappa B Signalling Activity. PLOS ONE, 10 (9), https://doi.org/10.1371/journal.pone.0138529.Access Status
Open AccessNHMRC Grant code
NHMRC/628858Abstract
Salmonella Typhimurium employs an array of type III secretion system effectors that facilitate intracellular survival and replication during infection. The Salmonella effector SseK3 was originally identified due to amino acid sequence similarity with NleB; an effector secreted by EPEC/EHEC that possesses N-acetylglucoasmine (GlcNAc) transferase activity and modifies death domain containing proteins to block extrinsic apoptosis. In this study, immunoprecipitation of SseK3 defined a novel molecular interaction between SseK3 and the host protein, TRIM32, an E3 ubiquitin ligase. The conserved DxD motif within SseK3, which is essential for the GlcNAc transferase activity of NleB, was required for TRIM32 binding and for the capacity of SseK3 to suppress TNF-stimulated activation of NF-κB pathway. However, we did not detect GlcNAc modification of TRIM32 by SseK3, nor did the SseK3-TRIM32 interaction impact on TRIM32 ubiquitination that is associated with its activation. In addition, lack of sseK3 in Salmonella had no effect on production of the NF-κB dependent cytokine, IL-8, in HeLa cells even though TRIM32 knockdown suppressed TNF-induced NF-κB activity. Ectopically expressed SseK3 partially co-localises with TRIM32 at the trans-Golgi network, but SseK3 is not recruited to Salmonella induced vacuoles or Salmonella induced filaments during Salmonella infection. Our study has identified a novel effector-host protein interaction and suggests that SseK3 may influence NF-κB activity. However, the lack of GlcNAc modification of TRIM32 suggests that SseK3 has further, as yet unidentified, host targets.
Export Reference in RIS Format
Endnote
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
Refworks
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References