The p38-interacting protein p38IP suppresses TCR and LPS signaling by targeting TAK1

ABSTRACT: Negative regulation of immunoreceptor signaling is required for preventing hyperimmune activation and maintaining immune homeostasis. The roles of p38IP in immunoreceptor signaling remain unclear. Here, we show that p38IP suppresses T-cell receptor (TCR)/LPS-activated NF-?B and p38 by targeting TAK1 kinase and that p38IP protein levels are downregulated in human-PBMCs from rheumatoid arthritis (RA) patients, inversely correlating with the enhanced activity of NF-?B and p38. Mechanistically, p38IP interacts with TAK1 to disassemble the TAK1-TAB (TAK1-binding protein) complex. p38IP overexpression decreases TCR-induced binding of K63-linked polyubiquitin (polyUb) chains to TAK1 but increases that to TAB2, and p38IP knockdown shows the opposite effects, indicating unanchored K63-linked polyUb

SUBMITTER: Prof. Yingqiu Li 

PROVIDER: S-SCDT-EMBOR-2019-48035V1 | biostudies-other |

REPOSITORIES: biostudies-other