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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
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
UBIQUITIN-BINDING, zinc finger, ubiquitin, TNFAIP3, NF-kappa B, A20, ASSEMBLY COMPLEX, CELLS, TNF, NEMO, INFLAMMATION, RECOGNITION, DEFICIENCY, PROTEIN, DOMAIN

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Citation

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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.
@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},
}

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