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A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7

Kelly Verhelst UGent, Isabelle Carpentier UGent, Marja Kreike UGent, Laura Meloni UGent, Lynn Verstrepen UGent, Tobias Kensche, Ivan Dikic and Rudi Beyaert UGent (2012) EMBO JOURNAL. 31(19). p.3845-3855
abstract
Linear polyubiquitination of proteins has recently been implicated in NF-kappa B signalling and is mediated by the linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP and Sharpin. However, the mechanisms that regulate linear ubiquitination are still unknown. Here, we show that A20 is rapidly recruited to NEMO and LUBAC upon TNF stimulation and that A20 inhibits LUBAC-induced NF-kappa B activation via its C-terminal zinc-finger 7 (ZF7) domain. Expression of a polypeptide corresponding to only ZF7 was sufficient to inhibit TNF-induced NF-kappa B activation. Both A20 and ZF7 can form a complex with NEMO and LUBAC, and are able to prevent the TNF-induced binding of NEMO to LUBAC. Finally, we show that ZF7 preferentially binds linear polyubiquitin chains in vitro, indicating A20-ZF7 as a novel linear ubiquitin-binding domain (LUBID). We thus propose a model in which A20 inhibits TNF- and LUBAC-induced NF-kappa B signalling by binding to linear polyubiquitin chains via its seventh zinc finger, which prevents the TNF-induced interaction between LUBAC and NEMO.
Please use this url to cite or link to this publication:
author
organization
alternative title
A20 inhibits LUBAC-mediated NF-kappa B activation by binding linear polyubiquitin chains via its zinc finger 7
year
type
journalArticle (original)
publication status
published
subject
keyword
UBIQUITIN-BINDING, zinc finger, ubiquitin, TNFAIP3, NF-kappa B, A20, ASSEMBLY COMPLEX, CELLS, TNF, NEMO, INFLAMMATION, RECOGNITION, DEFICIENCY, PROTEIN, DOMAIN
journal title
EMBO JOURNAL
Embo J.
volume
31
issue
19
pages
3845 - 3855
Web of Science type
Article
Web of Science id
000309656600009
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
9.822 (2012)
JCR rank
17/288 (2012)
JCR quartile
1 (2012)
ISSN
0261-4189
DOI
10.1038/emboj.2012.240
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3049338
handle
http://hdl.handle.net/1854/LU-3049338
date created
2012-11-08 13:17:34
date last changed
2014-05-12 11:01:51
@article{3049338,
  abstract     = {Linear polyubiquitination of proteins has recently been implicated in NF-kappa B signalling and is mediated by the linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP and Sharpin. However, the mechanisms that regulate linear ubiquitination are still unknown. Here, we show that A20 is rapidly recruited to NEMO and LUBAC upon TNF stimulation and that A20 inhibits LUBAC-induced NF-kappa B activation via its C-terminal zinc-finger 7 (ZF7) domain. Expression of a polypeptide corresponding to only ZF7 was sufficient to inhibit TNF-induced NF-kappa B activation. Both A20 and ZF7 can form a complex with NEMO and LUBAC, and are able to prevent the TNF-induced binding of NEMO to LUBAC. Finally, we show that ZF7 preferentially binds linear polyubiquitin chains in vitro, indicating A20-ZF7 as a novel linear ubiquitin-binding domain (LUBID). We thus propose a model in which A20 inhibits TNF- and LUBAC-induced NF-kappa B signalling by binding to linear polyubiquitin chains via its seventh zinc finger, which prevents the TNF-induced interaction between LUBAC and NEMO.},
  author       = {Verhelst, Kelly and Carpentier, Isabelle and Kreike, Marja and Meloni, Laura and Verstrepen, Lynn and Kensche, Tobias and Dikic, Ivan and Beyaert, Rudi},
  issn         = {0261-4189},
  journal      = {EMBO JOURNAL},
  keyword      = {UBIQUITIN-BINDING,zinc finger,ubiquitin,TNFAIP3,NF-kappa B,A20,ASSEMBLY COMPLEX,CELLS,TNF,NEMO,INFLAMMATION,RECOGNITION,DEFICIENCY,PROTEIN,DOMAIN},
  language     = {eng},
  number       = {19},
  pages        = {3845--3855},
  title        = {A20 inhibits LUBAC-mediated NF-\ensuremath{\kappa}B activation by binding linear polyubiquitin chains via its zinc finger 7},
  url          = {http://dx.doi.org/10.1038/emboj.2012.240},
  volume       = {31},
  year         = {2012},
}

Chicago
Verhelst, Kelly, Isabelle Carpentier, Marja Kreike, Laura Meloni, Lynn Verstrepen, Tobias Kensche, Ivan Dikic, and Rudi Beyaert. 2012. “A20 Inhibits LUBAC-mediated NF-κB Activation by Binding Linear Polyubiquitin Chains via Its Zinc Finger 7.” Embo Journal 31 (19): 3845–3855.
APA
Verhelst, K., Carpentier, I., Kreike, M., Meloni, L., Verstrepen, L., Kensche, T., Dikic, I., et al. (2012). A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7. EMBO JOURNAL, 31(19), 3845–3855.
Vancouver
1.
Verhelst K, Carpentier I, Kreike M, Meloni L, Verstrepen L, Kensche T, et al. A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7. EMBO JOURNAL. 2012;31(19):3845–55.
MLA
Verhelst, Kelly, Isabelle Carpentier, Marja Kreike, et al. “A20 Inhibits LUBAC-mediated NF-κB Activation by Binding Linear Polyubiquitin Chains via Its Zinc Finger 7.” EMBO JOURNAL 31.19 (2012): 3845–3855. Print.