Oncotarget

Research Papers:

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

Olga Sokolova _, Thilo Kähne, Kenneth Bryan and Michael Naumann

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2018; 9:14366-14381. https://doi.org/10.18632/oncotarget.24544

Metrics: PDF 1364 views  |   HTML 2285 views  |   ?  


Abstract

Olga Sokolova1, Thilo Kähne1, Kenneth Bryan2,3 and Michael Naumann1

1Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg 39120, Germany

2EMBL Australia Biomedical Informatics Group, Infection and Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia

3Present address: UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland

Correspondence to:

Olga Sokolova, email: [email protected]; [email protected]

Keywords: TAB; cytokines; innate immunity; TRIM; STOML2

Received: March 09, 2017     Accepted: February 10, 2018     Epub: February 21, 2018     Published: March 06, 2018

ABSTRACT

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 Helicobacter pylori or stimulated with the cytokines TNF and IL-1β. 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, IκB kinases IKKα/IKKβ and MAP kinases, NF-κB transactivation activity and IL-8 expression in the infected epithelial cells.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24544