Transcriptional activation of the tumor necrosis factor alpha-inducible zinc finger protein, A20, is mediated by kappa B elements.

Krikos, Alexandra; Laherty, Carol D.; Dixit, Vishva M.

doi:10.1016/s0021-9258(19)37138-8

Cited by 412 publications

(61 citation statements)

References 40 publications

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“…A20, encoded by the TNFα-induced protein 3 ( TNFAIP3 ) gene, is an OTU family DUB and one of the most extensively characterised negative feedback regulators of canonical NF-κB signalling. Most cell types exhibit low basal A20 expression [ 68 ] but it is strongly induced at the transcriptional level by NF-κB following stimulation with TNFα, IL-1 or LPS [ 69 , 70 ]. The N-terminal OTU domain of A20 exhibits DUB activity towards K48-, K11-, and to a lesser extent, K63-linked polyubiquitin chains in vitro [ 71 , 72 ].…”

Section: Inhibition Of Signalosome Complex Assemblymentioning

confidence: 99%

Inhibitory feedback control of NF-κB signalling in health and disease

Prescott¹,

Mitchell

Cook

2021

Biochemical Journal

113

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Cells must adapt to changes in their environment to maintain cell, tissue and organismal integrity in the face of mechanical, chemical or microbiological stress. Nuclear factor-κB (NF-κB) is one of the most important transcription factors that controls inducible gene expression as cells attempt to restore homeostasis. It plays critical roles in the immune system, from acute inflammation to the development of secondary lymphoid organs, and also has roles in cell survival, proliferation and differentiation. Given its role in such critical processes, NF-κB signalling must be subject to strict spatiotemporal control to ensure measured and context-specific cellular responses. Indeed, deregulation of NF-κB signalling can result in debilitating and even lethal inflammation and also underpins some forms of cancer. In this review, we describe the homeostatic feedback mechanisms that limit and ‘re-set’ inducible activation of NF-κB. We first describe the key components of the signalling pathways leading to activation of NF-κB, including the prominent role of protein phosphorylation and protein ubiquitylation, before briefly introducing the key features of feedback control mechanisms. We then describe the array of negative feedback loops targeting different components of the NF-κB signalling cascade including controls at the receptor level, post-receptor signalosome complexes, direct regulation of the critical ‘inhibitor of κB kinases’ (IKKs) and inhibitory feedforward regulation of NF-κB-dependent transcriptional responses. We also review post-transcriptional feedback controls affecting RNA stability and translation. Finally, we describe the deregulation of these feedback controls in human disease and consider how feedback may be a challenge to the efficacy of inhibitors.

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Section: Inhibition Of Signalosome Complex Assemblymentioning

confidence: 99%

Inhibitory feedback control of NF-κB signalling in health and disease

Prescott¹,

Mitchell

Cook

2021

Biochemical Journal

113

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“…One recent report shows that prolonged activation of JNK-1 is necessary for the TNF-induced initiation of apoptosis in rat mesangial cells and that a mitogen-activated phosphatase-1 may be involved in protecting cells from TNF-induced apoptosis by preventing prolonged JNK activation (57). We have previously shown that BHA inhibits TNF-induced cytotoxicity, but does not block the early TNF-induced NF-B activation in L929 cells (35) and WEHI cells (data not shown) which is involved in protective pathways against TNF cytotoxicity (7,60). In summary, the data presented strongly suggest that sPLA 2 and cPLA 2 do not mediate TNF-induced apoptosis in WEHI cells.…”

Section: Fig 5 Effect Of Increasing Concentrations Of Rtnf-␣ Agonisticmentioning

confidence: 96%

“…Binding of TNFR-associated factor 2 to the activated TNFR signals the activation of NF-B as well as c-Jun N-terminal kinase ( JNK), also called stressactivated protein kinase (SAPK), which seems to be separately regulated (6). Activation of B elements mediates the transcriptional activation of the zinc finger protein A20 (7), which protects against TNF-cytotoxicity. Manganous superoxide dismutase (8) and the major heat shock protein hsp70 (9) also protect against TNF-induced cytotoxicity.…”

mentioning

confidence: 99%

Specificity of endogenous fatty acid release during tumor necrosis factor-induced apoptosis in WEHI 164 fibrosarcoma cells

Brekke

Sagen

Bjerve

1999

Journal of Lipid Research

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Recombinant tumor necrosis factor alpha (rTNF-␣ )-induced release of endogenous fatty acids was examined in WEHI 164 clone 13 fibrosarcoma cells using a highly sensitive HPLC method. The initial rTNF-␣ -induced extracellular release of endogenous fatty acids was dominated by 20:4n-6, 22:4n-6, 24:4n-6, and 18:1n-9 showing relative rates of 2.9, 0.9, 1.1, and 1.0, respectively. Release of endogenous AA and DNA fragmentation occurred simultaneously and preceded cell death by approx. 2 h. Methyl arachidonoyl fluorophosphonate and LY311727, specific inhibitors of Ca 2 ؉ -dependent cytosolic PLA 2 (cPLA 2 ) and secretory PLA 2 (sPLA 2 ), respectively, neither blocked rTNF-␣ -induced cytotoxicity or endogenous AA release. However, both inhibitors reduced rTNF-␣ -induced release of other endogenous fatty acids. In comparison, the antioxidant butylated hydroxyanisole (BHA) completely inhibited the rTNF-␣ -induced cytotoxicity as well as AA release mediated through the TNF receptor p55, while the very similar antioxidant butylated hydroxytoluene had no effect. BHA did not inhibit recombinant cPLA 2 or sPLA 2 enzyme activity in vitro. Furthermore, stimulation of cells with rTNF-␣ for 4 h did not increase cPLA 2 enzyme activity. The data indicate that neither cPLA 2 or sPLA 2 mediate rTNF-␣ -induced apoptosis and extracellular AA release in WEHI cells. The results suggest that a BHA-sensitive signaling pathway coupled to AA release is a key event in TNF-induced cytotoxicity in these cells. -Brekke, O-L., E. Sagen, and K. S. Bjerve. Specificity of endogenous fatty acid release during tumor necrosis factor-induced apoptosis in WEHI 164 fibrosarcoma cells.

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“…The A20 protein is encoded by the Tnfaip3 gene, and it harbors both DUB activity and E3 ligase activity [207]. A20 is strongly induced upon TNF signaling, and potently inhibits NFκB signaling [208]. Tnfaip3-deficient mice suffer from spontaneous inflammation, cachexia and die prematurely, due to the inability of Tnfaip3-deficient cells to terminate TNF-induced NFκB activity [209].…”

Section: Negative Regulation Of Rip1mentioning

confidence: 99%

Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination

Budroni

Versteeg

2021

Viruses

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The rapid and dynamic activation of the innate immune system is achieved through complex signaling networks regulated by post-translational modifications modulating the subcellular localization, activity, and abundance of signaling molecules. Many constitutively expressed signaling molecules are present in the cell in inactive forms, and become functionally activated once they are modified with ubiquitin, and, in turn, inactivated by removal of the same post-translational mark. Moreover, upon infection resolution a rapid remodeling of the proteome needs to occur, ensuring the removal of induced response proteins to prevent hyperactivation. This review discusses the current knowledge on the negative regulation of innate immune signaling pathways by deubiquitinating enzymes, and through degradative ubiquitination. It focusses on spatiotemporal regulation of deubiquitinase and E3 ligase activities, mechanisms for re-establishing proteostasis, and degradation through immune-specific feedback mechanisms vs. general protein quality control pathways.

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Transcriptional activation of the tumor necrosis factor alpha-inducible zinc finger protein, A20, is mediated by kappa B elements.

Cited by 412 publications

References 40 publications

Inhibitory feedback control of NF-κB signalling in health and disease

Inhibitory feedback control of NF-κB signalling in health and disease

Specificity of endogenous fatty acid release during tumor necrosis factor-induced apoptosis in WEHI 164 fibrosarcoma cells

Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination

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