Destroying Tolls

Honey, Karen

doi:10.1038/nri1387

Research Highlight
Published: 01 June 2004

Innate immunity

Destroying Tolls

Karen Honey

Nature Reviews Immunology volume 4, page 405 (2004)Cite this article

599 Accesses
Metrics details

Access through your institution

Buy or subscribe

Ubiquitin targeting of proteins for proteolytic degradation is a three-step process. First, ubiquitin is activated by a ubiquitin-activating enzyme (E1); second, activated ubiquitin is transferred to a ubiquitin-conjugating enzyme (E2 or UBC); and third, an E3 ubiquitin ligase attaches ubiquitin to lysine residues on the protein to be targeted for degradation.

Chuang and Ulevitch reasoned that the cytoplasmic Toll/interleukin-1-receptor (TIR) domain of TLRs, which is crucial for recruiting proteins involved in TLR signalling, might also bind proteins involved in negatively regulating TLRs. Using a yeast two-hybrid approach, they found that the TIR domain of human TLR9 binds a previously described protein known as TRIAD3. This interaction was not specific for the TIR domain of TLR9, as TRIAD3 also interacted with TLR3, TLR4 and TLR5, but it did not interact with TLR2.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

Purchase on SpringerLink
Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

ORIGINAL RESEARCH PAPER

Chuang, T. & Ulevitch, R. J. Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nature Immunol. 25 April 2004 (doi:10.1038/ni1066)

Download references

Authors