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

Oncogene
S WagnerR Beyaert

Abstract

Deregulated nuclear factor kappaB (NF-kappaB) activation plays an important role in inflammation and tumorigenesis. ABIN proteins have been characterized as negative regulators of NF-kappaB signaling. However, their mechanism of NF-kappaB 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-kappaB essential modulator/IkappaB kinase gamma (NEMO/IKKgamma) 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-kappaB inhibitory potential of ABINs. Taken together, these data illustrate an important role for ubiquitin bindi...Continue Reading

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Citations

Dec 17, 2011·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Yusuke SakaiHiroyuki Nakayama
Mar 14, 2009·Chemical Reviews·Yu-Hsin ChiuZhijian J Chen
Apr 30, 2010·Nature·Hirofumi MaruyamaHideshi Kawakami
Jul 21, 2011·Nature Immunology·Jürgen Ruland
Oct 13, 2012·Nature Reviews. Immunology·Averil Ma, Barbara A Malynn
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Aug 31, 2013·Nature Reviews. Molecular Cell Biology·Kristopher ClarkPhilip Cohen
Sep 3, 2011·The Journal of Biological Chemistry·Linlin GaoEdward W Harhaj
Mar 3, 2009·The Journal of Biological Chemistry·Michael E FrenchLinda Hicke
Nov 15, 2008·The Journal of Biological Chemistry·Beatrice CoornaertRudi Beyaert
May 25, 2011·The Journal of Experimental Medicine·Sambit K NandaPhilip Cohen
Mar 20, 2010·Cold Spring Harbor Perspectives in Biology·Alain Israël
Apr 22, 2009·Molecular and Cellular Biology·Suzanne PazJohn Hiscott
Mar 7, 2012·Microbiology and Molecular Biology Reviews : MMBR·Jonathan Maelfait, Rudi Beyaert
Mar 24, 2009·Annual Review of Immunology·Sivakumar Vallabhapurapu, Michael Karin
Jun 7, 2011·Arthritis Research & Therapy·Geert van Loo, Rudi Beyaert
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May 1, 2012·Trends in Cell Biology·Kazuhiro Iwai
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Oct 18, 2011·Biochimica Et Biophysica Acta·Igor GurevichBrian J Aneskievich
May 7, 2011·Trends in Biochemical Sciences·Lynn VerstrepenRudi Beyaert

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