Heyninck, K. & Beyaert, R. The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-B activation at the level of TRAF6. FEBS Lett. 442, 147−150

Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Belgium.
FEBS Letters (Impact Factor: 3.17). 02/1999; 442(2-3):147-50. DOI: 10.1016/S0014-5793(98)01645-7
Source: PubMed


The zinc finger protein A20 is encoded by an immediate early response gene whose expression is induced by different inflammatory stimuli, including interleukin-1 (IL-1). Gene induction by IL-1 is mediated by activation of the transcription factor NF-kappaB, and requires the signal adapter protein TRAF6. The latter interacts with the NF-kappaB-inducing kinase NIK, which is believed to be part of the IkappaB kinase complex. Expression of A20 potently inhibits IL-1-induced NF-kappaB activation by an unknown mechanism. Inhibition of IL-1-induced NF-kappaB activation was found to be mediated by the C-terminal zinc finger-containing domain of A20. More importantly, we present evidence that A20 interferes with IL-1-induced NF-kappaB activation at the level of TRAF6, upstream of NIK. Moreover, A20 was shown to directly interact with TRAF6.

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Available from: Karen Heyninck, Jan 02, 2014
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    • "For example, the RIG-I protein is down regulated by the host protein RFN125, CYLD, NLRC5, Casein kinase II and other kinases [20], [21], [22], [23], [24], [25]; the MAVS protein is also negatively regulated by the host proteins NLRX1 and PCBP2 [26], [27], and is cleaved from the mitochondria surface by the NS3/4 protease of the hepatitis C virus (HCV) [28]. Moreover, the adaptor proteins TRAF3 and TRAF6 are targeted by the cellular proteins DUBA and A20 [29], [30], and TBK1 is sequestered by SIKE [31]. The transcription activator IRF3 is under negative regulation by host protein Pin1 and MafB, and HIV accessory proteins VPR and Vif [32], [33], [34], and the p65 subunit of NFκB is targeted for degradation by PDLIM2 [35]. "
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    Preview · Article · Jun 2011 · PLoS ONE
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    • "The signaling abilities of several members of the NGF/TNF receptor family can be modulated by the interaction of their effectors with other cellular proteins. I-TRAF and A20 can interact with several TRAF proteins and repress NF-kB induction in response to TNF-a or IL-1 (Rothe et al. 1996) (Song et al. 1996) (Heyninck and Beyaert 1999). "
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    • "One reason for the more tissue-restricted phenotype of TAX1BP1-deficient mice might be the redundancy with other A20 adaptor proteins. In this context, A20 has been shown to bind three different ABIN family members, which have been suggested to be involved in the NF-kB inhibitory function of A20 (Heyninck and Beyaert, 1999; Van Huffel et al, 2001; Wullaert et al, 2007). Moreover, ABIN-1 was recently shown to facilitate the binding of A20 to NEMO and to be essential for NEMO de-ubiquitination by A20 (Mauro et al, 2006). "
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