PuSH - Publication Server of Helmholtz Zentrum München

Hadian, K. ; Griesbach, R.A. ; Dornauer, S. ; Wanger, T.M. ; Nagel, D. ; Metlitzky, M. ; Beisker, W. ; Schmidt-Supprian, M.* ; Krappmann, D.

NF-κB essential modulator (NEMO) interaction with linear and Lys-63 ubiquitin chains contributes to NF-κB activation.

J. Biol. Chem. 286, 26107-26117 (2011)
Publ. Version/Full Text Volltext DOI PMC
Free by publisher
Open Access Green as soon as Postprint is submitted to ZB.
The IκB kinase (IKK) complex acts as a gatekeeper of canonical NF-κB signaling in response to upstream stimulation. IKK activation requires sensing of ubiquitin chains by the essential IKK regulatory subunit IKKγ/NEMO. However, it has remained enigmatic whether NEMO binding to Lys-63-linked or linear ubiquitin chains is critical for triggering IKK activation. We show here that the NEMO C terminus, comprising the ubiquitin binding region and a zinc finger, has a high preference for binding to linear ubiquitin chains. However, immobilization of NEMO, which may be reminiscent of cellular oligomerization, facilitates the interaction with Lys-63 ubiquitin chains. Moreover, selective mutations in NEMO that abolish association with linear ubiquitin but do not affect binding to Lys-63 ubiquitin are only partially compromising NF-κB signaling in response to TNFα stimulation in fibroblasts and T cells. In line with this, TNFα-triggered expression of NF-κB target genes and induction of apoptosis was partially compromised by NEMO mutations that selectively impair the binding to linear ubiquitin chains. Thus, in vivo NEMO interaction with linear and Lys-63 ubiquitin chains is required for optimal IKK activation, suggesting that both type of chains are cooperating in triggering canonical NF-κB signaling.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords polyubiquitin chains; assembly complex; ikk complex; stem-cells; tnf-alpha; binding; component; domain; oligomerization; recognition
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Journal Journal of Biological Chemistry, The
Quellenangaben Volume: 286, Issue: 29, Pages: 26107-26117 Article Number: , Supplement: ,
Publisher American Society for Biochemistry and Molecular Biology
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOX)