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Interactome analysis of transforming growth factor-?-activated kinase 1 in Helicobacter pylori-infected cells revealed novel regulators tripartite motif 28 and CDC37.


ABSTRACT: Transforming growth factor-? (TGF?)-activated kinase 1 (TAK1) plays a central role in controlling the cellular pro-inflammatory response via the activation of the nuclear factor ?B (NF-?B)- and mitogen-activated protein (MAP) kinases-dependent transcriptional programs. Here, we show that depletion of TAK1 and the TAK1-binding proteins TAB1 and TAB2 affects NF-?B, JNK and p38 phosphorylation and suppresses NF-?B activity in AGS cells infected with Helicobacter pylori or stimulated with the cytokines TNF and IL-1?. To increase our understanding of TAK1 regulation and function, we performed mass spectrometry (MS)-based TAK1 interactomics. In addition to the identification of known and novel TAK1 interacting proteins, including TRIM28, CDC37 and STOML2, analysis of the MS data revealed various post-translational modifications within the TAK1/TAB complex. By applying siRNAs, TRIM28 and CDC37 were found to regulate phosphorylations of TAK1, I?B kinases IKK?/IKK? and MAP kinases, NF-?B transactivation activity and IL-8 expression in the infected epithelial cells.

SUBMITTER: Sokolova O 

PROVIDER: S-EPMC5865676 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Interactome analysis of transforming growth factor-β-activated kinase 1 in <i>Helicobacter pylori</i>-infected cells revealed novel regulators tripartite motif 28 and CDC37.

Sokolova Olga O   Kähne Thilo T   Bryan Kenneth K   Naumann Michael M  

Oncotarget 20180221 18


Transforming growth factor-β (TGFβ)-activated kinase 1 (TAK1) plays a central role in controlling the cellular pro-inflammatory response via the activation of the nuclear factor κB (NF-κB)- and mitogen-activated protein (MAP) kinases-dependent transcriptional programs. Here, we show that depletion of TAK1 and the TAK1-binding proteins TAB1 and TAB2 affects NF-κB, JNK and p38 phosphorylation and suppresses NF-κB activity in AGS cells infected with <i>Helicobacter pylori</i> or stimulated with the  ...[more]

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