Selective binding of linear ubiquitin chains to NEMO in NF-kappaB activation

Fumiyo Ikeda, Simin Rahighi, Soichi Wakatsuki, Ivan Dikic

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Citations (Scopus)


Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) depends on multiple ubiquitination and phosphorylation signals. For example, an acute stimulation of cells with variety of cytokines leads to Lys63-linked ubiquitin chain conjugation on the receptor-associated complexes to activate the TAK1 kinase. In addition, function of the linear ubiquitin chain assembly (LUBAC) ligase is required for the activation of IkappaB kinase complex (IKK), which in turn phosphorylates IkappaB-alpha and causes its proteasomal degradation via Lys48-linked ubiquitin-chain conjugation. The directionality and the specificity in the NF-kappaB pathway are accomplished by the specific ubiquitin receptors that are able to recognize specific ubiquitin signals. We have provided structural and biochemical evidences for a selective binding of the NEMO-UBAN (Ubiquitin Binding in ABIN and NEMO) motif to linear (head-to-tail) ubiquitin chains. The NEMO-UBAN forms a parallel coiled-coil dimer, which binds to two linear diubiquitin molecules perpendicularly positioned on each side of the NEMO dimer. Residues of NEMO involved in binding to linear ubiquitin chains are essential for NF-kappaB activation by TNF-alpha and other agonists and are found mutated in human disease characterized by ectodermal dysplasia with immunodeficiency.

Original languageEnglish
Title of host publicationAdvances in TNF Family Research
Subtitle of host publicationProceedings of the 12th International TNF Conference, 2009
EditorsDavid Wallach, Andrew Kovalenko, Marc Feldmann
Number of pages8
Publication statusPublished - 2011
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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