Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Mar 27;284(13):8211-5.
doi: 10.1074/jbc.R800038200. Epub 2008 Aug 6.

Role of non-degradative ubiquitination in interleukin-1 and toll-like receptor signaling

Sinéad E Keating  1 , Andrew G Bowie
Affiliations
Review

Role of non-degradative ubiquitination in interleukin-1 and toll-like receptor signaling

Sinéad E Keating et al. J Biol Chem. .
No abstract available

PubMed Disclaimer

Figures

FIGURE 1.
FIGURE 1.
Role of Lys63-linked polyubiquitination in IL-1R/TLR signaling to NF-κB. IL-1R/TLR stimulation leads to receptor dimerization, allowing recruitment of the appropriate downstream TIR adaptor via TIR/TIR domain associations. This is followed by activation of IRAK-1 and IRAK-2. IRAK-1 activation involves phosphorylation by IRAK-4, but this has yet to be confirmed for IRAK-2. IRAK-2 triggers the E3 ligase activity of TRAF6, potentially by promoting its oligomerization, leading to TRAF6 autoubiquitination and the synthesis of Lys63-linked polyubiquitin chains on target molecules such as NEMO. TAB2 (or TAB3) specifically recognizes Lys63-linked polyubiquitin chains on TRAF6, thus recruiting TAK1 to the TRAF6 complex, resulting in TAK1 activation. In parallel, Pellino proteins are phosphorylated by IRAK-1, a process that results in their degradation. However, the Pellino proteins also mediate Lys63-linked polyubiquitination of IRAK-1, facilitating the recruitment of NEMO and therefore the IKK complex through the specific recognition of these ubiquitin (Ub) modifications. Activated TAK1, now in close proximity to the IKK complex, phosphorylates and activates this complex. Red arrows indicate recruitment via binding to polyubiquitin chains.
See this image and copyright information in PMC

References

    1. Akira, S., Uematsu, S., and Takeuchi, O. (2006) Cell 124 783–801 - PubMed
    1. Meylan, E., and Tschopp, J. (2006) Mol. Cell 22 561–569 - PubMed
    1. Unterholzner, L., and Bowie, A. G. (2008) Biochem. Pharmacol. 75 589–602 - PubMed
    1. Thompson, A. J., and Locarnini, S. A. (2007) Immunol. Cell Biol. 85 435–445 - PubMed
    1. Haas, T., Metzger, J., Schmitz, F., Heit, A., Muller, T., Latz, E., and Wagner, H. (2008) Immunity 28 315–323 - PubMed

LinkOut - more resources