Targeting of TAK1 by the NF-κB protein Relish regulates the JNK-mediated immune response in Drosophila

Abstract

The molecular circuitry underlying innate immunity is constructed of multiple, evolutionarily conserved signaling modules with distinct regulatory targets. The MAP kinases and the IKK-NF-B molecules play important roles in the initiation of immune effector responses. We have found that the Drosophila NF-B protein Relish plays a crucial role in limiting the duration of JNK activation and output in response to Gram-negative infections. Relish activation is linked to proteasomal degradation of TAK1, the upstream MAP kinase kinase kinase required for JNK activation. Degradation of TAK1 leads to a rapid termination of JNK signaling, resulting in a transient JNK-dependent response that precedes the sustained induction of Relish-dependent innate immune loci. Because the IKK-NF-B module also negatively regulates JNK activation in mammals, thereby controlling inflammation-induced apoptosis, the regulatory cross-talk between the JNK and NF-B pathways appears to be broadly conserved.

Reactive oxygen species mediate crosstalk between NF-κB and JNK

“…The biological consequences of the JNK pathway (DJNK) in Drosophila are less complicated than in mammals, functioning to preferentially promote apoptosis. Park et al 42 demonstrated that JNK activation is prolonged in S2 cells lacking Relish. Moreover, they showed that Relish activation leads to degradation of TAK1, resulting in termination of JNK signaling.…”

Bim and Noxa Are Candidates to Mediate the Deleterious Effect of the NF-κB Subunit RelA in Cerebral Ischemia

“…IKK has been shown to inhibit the transcription factor FOXO3a (Hu et al, 2004), which stimulates Bim gene transcription (Gilley et al, 2003;Sunters et al, 2003). Likewise, NF-B inhibits the effect of JNK on gene transcription (De Smaele et al, 2001;Tang et al, 2001;Park et al, 2004). JNK has been shown to control Bim transcription in cerebral ischemia (Kuan et al, 2003;Okuno et al, 2004).…”

Differential immune responses of Monochamus alternatus against symbiotic and entomopathogenic fungi

“…TAK, a MAPKKK, functions upstream of the IKK and downstream of IMD, a receptor interacting protein (De Gregorio et al, 2002;Lemaitre, 2004). In general, JNK and JAK/STAT pathway also could regulate AMPs (Garver et al, 2013;Park et al, 2004).…”