A20 INHIBITS NF-κB ACTIVATION DOWNSTREAM OF MULTIPLE MAP3 KINASES AND INTERACTS WITH THE IκB SIGNALOSOME
2001; Elsevier BV; Volume: 15; Issue: 6 Linguagem: Inglês
10.1006/cyto.2001.0921
ISSN1096-0023
AutoresFiras S. Zetoune, Anita R. Murthy, Zhihong Shao, Tom Hlaing, Michael G. Zeidler, Yong Li, Claudius Vincenz,
Tópico(s)Cytokine Signaling Pathways and Interactions
ResumoA20, a TNF inducible gene, inhibits TNF-mediated apoptosis as well as NF-kappa B induced by this cytokine. Reporter assay experiments revealed that A20 is a very effective inhibitor of NF-kappa B signaling induced by TRAFs and several Map3 kinases, including NIK, MEKK1, COT, and TAK1. Similarly, the NF-kappa B inducing activity of TAX, an activator of the I kappa B kinase complex, is also abrogated by A20. Inhibition of NF-kappa B is specific as A20 has no effect on TNF-alpha-induced JNK activation. These results suggest that the molecular target of A20 is more distal to the receptor than TRAFs as previously proposed. A20 inhibits NF-kappa B-dependent transcription without a concomitant decrease in nuclear NF-kappa B DNA binding activity or nuclear translocation of p65. This apparent discrepancy between transcriptional readout and gel shift experiments is observed with a variety of stimuli, including expression of IKK beta. Therefore, in addition to the phosphorylation of I kappa B, another signal is needed for transcriptional activation of NF-kappa B. A20 inhibits this non-redundant signal. The observation that A20 associates with IKK alpha and is phosphorylated upon IKK beta co-expression may suggest that A20 interferes with some aspects of signalosome function.
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