Abstract
Enterohemorrhagic Escherichia coli (EHEC) utilizes a type III secretion system (T3SS) to inject effector proteins into host cells. The EHEC NleH1 effector inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reducing the nuclear translocation of the ribosomal protein S3 (RPS3). NleH1 prevents RPS3 phosphorylation by the IκB kinase-β (IKKβ). IKKβ is a central kinase in the NF-κB pathway, yet NleH1 only restricts the phosphorylation of a subset of the IKKβ substrates. We hypothesized that a protein cofactor might dictate this inhibitory specificity. We determined that heat shock protein 90 (Hsp90) interacts with both IKKβ and NleH1 and that inhibiting Hsp90 activity reduces RPS3 nuclear translocation.
Highlights
The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family of transcription factors regulates innate and adaptive immune responses
We identified heat shock protein 90 (Hsp90), Cell division cycle protein 37 (Cdc37) and ribosomal protein S3 (RPS3) in these samples
3 of 9to the complex with2018, IKK, which important association between Hsp90 and IKK, we focused on the potential interactions between complex with IKK, which plays a critical role in its activation and regulation [10,11]
Summary
The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family of transcription factors regulates innate and adaptive immune responses. Activation of NF-κB signaling is initiated by external stimuli that activate the IκB kinase (IKK) complex. This complex consists of two catalytic components, IKKα (IKK1) and IKKβ (IKK2), in addition to a regulatory subunit, the NF-κB Essential. EHEC encodes two forms of the NleH effector, NleH1 and NleH2 [5,6] Both effectors bind RPS3, but only NleH1 inhibits RPS3 nuclear translocation by preventing RPS3 phosphorylation on S209 by IKKβ [4,5]. We identified heat shock protein 90 (Hsp90) as an NleH1 binding partner and found that inhibiting Hsp activity reduced RPS3 nuclear translocation.
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