Selective Binding of Linear Ubiquitin Chains to NEMO in NF-kappaB Activation

  • Fumiyo Ikeda
  • Simin Rahighi
  • Soichi Wakatsuki
  • Ivan Dikic
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)


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.


Ectodermal Dysplasia Ubiquitin Chain Ubiquitin Binding Ubiquitin Binding Domain Ubiquitin Signal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by grants from Deutsche Forschungsgemeinschaft, the Cluster of Excellence “Macromolecular Complexes” of the Goethe University Frankfurt (EXC115) to ID, and partly by Grant-in-Aid for Scientific Research from the MEXT to MK and Target Protein Research Program of the MEXT to SW. FI is supported by JSPS Postdoctoral Fellowships for Research Abroad.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Fumiyo Ikeda
    • 1
  • Simin Rahighi
    • 2
    • 3
  • Soichi Wakatsuki
    • 2
    • 3
  • Ivan Dikic
    • 1
  1. 1.Institute of Biochemistry II and Cluster of Excellence Frankfurt, Goethe University School of MedicineFrankfurt(Main)Germany
  2. 2.Structural Biology Research CenterPhoton Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), TsukubaIbarakiJapan
  3. 3.Graduate University for Advanced Studies, HayamaKanagawaJapan

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