TBK1-associated Protein in Endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways

Chun Hung Chang, Li Chun Lai, Hung Chi Cheng, Kuan Ru Chen, Ying Zhang Syue, Hsueh Chi Lu, Wan Ying Lin, Shun Hua Chen, Huei Sheng Huang, Ai Li Shiau, Huan Yao Lei, Jun Qin, Pin Ling

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways.Wefound that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-β and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-β induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-β. TAPE knockdown failed to block Trif-mediated IFN-β induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-β induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step.

Original languageEnglish
Pages (from-to)7043-7051
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number9
DOIs
Publication statusPublished - 2011 Mar 4

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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