STRAP Acts as a Scaffolding Protein in Controlling the TLR2/4 Signaling Pathway

Hyunbin D. Huh, Eun A. Ra, Taeyun A. Lee, Sujin Kang, Areum Park, Eunhye Lee, Junhee L. Choi, Eunji Jang, Ji Eun Lee, Sungwook Lee, Boyoun Park

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The WD40-repeat protein serine/threonine kinase receptor-associated protein (STRAP) is involved in the regulation of several biological processes, including cell proliferation and apoptosis, in response to various stresses. Here, we show that STRAP is a new scaffold protein that functions in Toll-like receptor (TLR)-mediated immune responses. STRAP specifically binds transforming growth factor β-activated kinase 1 (TAK1) and Iκ B kinase alpha (IKKα) along with nuclear factor-κ B (NF-κ B) subunit p65, leading to enhanced association between TAK1, IKKα, and p65, and subsequent facilitation of p65 phosphorylation and nuclear translocation. Consequently, the depletion of STRAP severely impairs interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-1β production, whereas its overexpression causes a significant increase in the secretion of these pro-inflammatory cytokines by TLR2 or TLR4 agonist-stimulated macrophages. Notably, STRAP translocates to the nucleus and subsequently binds to NF-κ B at later times after lipopolysaccharide (LPS) stimulation, resulting in prolonged IL-6 mRNA production. Moreover, the C-terminal region of STRAP is essential for its functional activity in facilitating IL-6 production. Collectively, these observations suggest that STRAP acts as a scaffold protein that positively contributes to innate host defenses against pathogen infections.

Original languageEnglish
Article number38849
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Dec 9

    Fingerprint

All Science Journal Classification (ASJC) codes

  • General

Cite this

Huh, H. D., Ra, E. A., Lee, T. A., Kang, S., Park, A., Lee, E., Choi, J. L., Jang, E., Lee, J. E., Lee, S., & Park, B. (2016). STRAP Acts as a Scaffolding Protein in Controlling the TLR2/4 Signaling Pathway. Scientific reports, 6, [38849]. https://doi.org/10.1038/srep38849