The zinc finger of NEMO is a functional ubiquitin-binding domain.
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Cordier F, Grubisha O, Traincard F, Veron M, Delepierre M, Agou F
The zinc finger of NEMO is a functional ubiquitin-binding domain.
J Biol Chem. 2009 Jan 30;284(5):2902-7. doi: 10.1074/jbc.M806655200. Epub 2008 Nov 25.
- PubMed ID
- 19033441 [ View in PubMed]
- 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.