2. Academic Validation
  3. The zinc finger of NEMO is a functional ubiquitin-binding domain

The zinc finger of NEMO is a functional ubiquitin-binding domain

  • J Biol Chem. 2009 Jan 30;284(5):2902-2907. doi: 10.1074/jbc.M806655200.
Florence Cordier 1,  Olivera Grubisha 2,  François Traincard 2,  Michel Véron 2,  Muriel Delepierre 3,  Fabrice Agou 4
Affiliations

Affiliations

  • 1 Institut Pasteur, UnitédeRésonance Magnétique Nucleaire des Biomolécules, 25/28 rue du Dr. Roux, F-75015 Paris, France. Electronic address: fcordier@pasteur.fr.
  • 2 Institut Pasteur, Unité de Biochimie Structurale et Cellulaire, CNRS, URA 2185, 25/28 rue du Dr. Roux, F-75015 Paris, France.
  • 3 Institut Pasteur, UnitédeRésonance Magnétique Nucleaire des Biomolécules, 25/28 rue du Dr. Roux, F-75015 Paris, France.
  • 4 Institut Pasteur, Unité de Biochimie Structurale et Cellulaire, CNRS, URA 2185, 25/28 rue du Dr. Roux, F-75015 Paris, France. Electronic address: fagou@pasteur.fr.
PMID: 19033441 DOI: 10.1074/jbc.M806655200
Abstract

NEMO (NF-kappaB essential modulator) is a regulatory protein essential to the canonical NF-kappaB signaling pathway, notably involved in immune and inflammatory responses, Apoptosis, and oncogenesis. Here, we report that the zinc finger (ZF) motif, located in the regulatory C-terminal half of NEMO, forms a specific complex with ubiquitin. We have investigated the NEMO ZF-ubiquitin interaction and proposed a structural model of the complex based on NMR, fluorescence, and mutagenesis data and on the sequence homology with the polymerase eta ubiquitin-binding zinc finger involved in DNA repair. Functional complementation assays and in vivo pull-down experiments further show that ZF residues involved in ubiquitin binding are functionally important and required for NF-kappaB signaling in response to tumor necrosis factor-alpha. Thus, our findings indicate that NEMOZFisa bona fide ubiquitin-binding domain of the ubiquitin-binding zinc finger type.

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