Gene interactions and pathways from curated databases and text-mining
Blood 2005, PMID: 15755895

Balance between NF-kappaB and JNK/AP-1 activity controls dendritic cell life and death.

Kriehuber, Ernst; Bauer, Wolfgang; Charbonnier, Anne-Sophie; Winter, Dorian; Amatschek, Stefan; Tamandl, Dietmar; Schweifer, Norbert; Stingl, Georg; Maurer, Dieter

The life cycle of dendritic cells (DCs) must be precisely regulated for proper functioning of adaptive immunity. However, signaling pathways actively mediating DC death remain enigmatic. Here we describe a novel mechanism of hierarchical transcriptional control of DC life and death. Ligation of tumor necrosis factor receptor superfamily (TNFR-SF) members on DCs and cognate contact with T cells resulted in quantitatively balanced nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK)-mediated activator protein-1 (AP-1) induction and strongly enhanced DC longevity. Specific blockade of NF-kappaB in DCs induced strongly augmented JNK/AP-1 activity because of elevated levels of reactive oxygen species. In this scenario, DC activation by TNFR-SF members or T cells induced DC apoptosis. Specific inhibition of JNK/AP-1 rescued DCs from this activation-induced cell death program and restored TNFR-SF member- and T-cell-mediated survival. We conclude that JNK/AP-1 activity is under negative feedback control of NF-kappaB and can execute apoptosis in DCs. Thus, feedback-controlled signaling amplitudes of 2 transcriptional pathways decide the fate of a DC.

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Text Mining Data

activator protein-1 (AP-1) → c-Jun N-terminal kinase (JNK): " Ligation of tumor necrosis factor receptor superfamily ( TNFR-SF ) members on DCs and cognate contact with T cells resulted in quantitatively balanced nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK) mediated activator protein-1 (AP-1) induction and strongly enhanced DC longevity "

activator protein-1 (AP-1) → nuclear factor-kappaB (NF-kappaB): " Ligation of tumor necrosis factor receptor superfamily ( TNFR-SF ) members on DCs and cognate contact with T cells resulted in quantitatively balanced nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK) mediated activator protein-1 (AP-1) induction and strongly enhanced DC longevity "

Manually curated Databases

No curated data.