Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins

S. Wagner, I. Carpentier, V. Rogov, M. Kreike, F. Ikeda, F. Löhr, C. J. Wu, J. D. Ashwell, V. Dötsch, I. Dikic, R. Beyaert

Research output: Contribution to journalArticle

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Abstract

Deregulated nuclear factor κB (NF-κB) activation plays an important role in inflammation and tumorigenesis. ABIN proteins have been characterized as negative regulators of NF-κB signaling. However, their mechanism of NF-κB inhibition remained unclear. With the help of a yeast two-hybrid screen, we identified ABIN proteins as novel ubiquitin-interacting proteins. The minimal ubiquitin-binding domain (UBD) corresponds to the ABIN homology domain 2 (AHD2) and is highly conserved in ABIN-1, ABIN-2 and ABIN-3. Moreover, this region is also present in NF-κB essential modulator/IκB kinase γ (NEMO/IKKγ) and the NEMO-like protein optineurin, and is therefore termed UBD in ABIN proteins and NEMO (UBAN). Nuclear magnetic resonance studies of the UBAN domain identify it as a novel type of UBD, with the binding surface on ubiquitin being significantly different from the binding surface of other UBDs. ABIN-1 specifically binds ubiquitinated NEMO via a bipartite interaction involving its UBAN and NEMO-binding domain. Mutations in the UBAN domain led to a loss of ubiquitin binding and impaired the NF-κB inhibitory potential of ABINs. Taken together, these data illustrate an important role for ubiquitin binding in the negative regulation of NF-κB signaling by ABINs and identify UBAN as a novel UBD.

Original languageEnglish
Pages (from-to)3739-3745
Number of pages7
JournalOncogene
Volume27
Issue number26
DOIs
Publication statusPublished - Jun 12 2008
Externally publishedYes

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Ubiquitin
Proteins
Carcinogenesis
Phosphotransferases
Magnetic Resonance Spectroscopy
Yeasts
Inflammation
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Wagner, S., Carpentier, I., Rogov, V., Kreike, M., Ikeda, F., Löhr, F., ... Beyaert, R. (2008). Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins. Oncogene, 27(26), 3739-3745. https://doi.org/10.1038/sj.onc.1211042

Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins. / Wagner, S.; Carpentier, I.; Rogov, V.; Kreike, M.; Ikeda, F.; Löhr, F.; Wu, C. J.; Ashwell, J. D.; Dötsch, V.; Dikic, I.; Beyaert, R.

In: Oncogene, Vol. 27, No. 26, 12.06.2008, p. 3739-3745.

Research output: Contribution to journalArticle

Wagner, S, Carpentier, I, Rogov, V, Kreike, M, Ikeda, F, Löhr, F, Wu, CJ, Ashwell, JD, Dötsch, V, Dikic, I & Beyaert, R 2008, 'Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins', Oncogene, vol. 27, no. 26, pp. 3739-3745. https://doi.org/10.1038/sj.onc.1211042
Wagner S, Carpentier I, Rogov V, Kreike M, Ikeda F, Löhr F et al. Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins. Oncogene. 2008 Jun 12;27(26):3739-3745. https://doi.org/10.1038/sj.onc.1211042
Wagner, S. ; Carpentier, I. ; Rogov, V. ; Kreike, M. ; Ikeda, F. ; Löhr, F. ; Wu, C. J. ; Ashwell, J. D. ; Dötsch, V. ; Dikic, I. ; Beyaert, R. / Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins. In: Oncogene. 2008 ; Vol. 27, No. 26. pp. 3739-3745.
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