Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the androgen-independent prostate cancer cells DU145, despite expressing Fas and FasL, were resistant to anti-Fas-induced apoptosis, and that this resistance could be overcome by pretreating the cells with sublethal doses of camptothecin. Here, we provide evidence that SAPK/JNK activity is required for camptothecin sensitization to anti-Fas-induced apoptosis. Camptothecin, but not Fas ligation, was shown to activate SAPK/JNK in a time-dependent manner, and to induce c-Jun expression. The effects were more prominent in cells treated with both camptothecin and anti-Fas. The expression levels of MKP-1, a phosphatase which regulates SAPK/JNK and which has been implicated in prostate cancer resistance to apoptosis, remained unchanged. Inhibition of caspases had no effect on the SAPK/JNK activation, suggesting that this activation is an upstream event in the Fas-signalling pathway, and is independent of caspase activity. Antisense oligonucleotides targeted to JNK1 and JNK2 reversed the effect of camptothecin. These results suggest that stress kinase activation can significantly influence the fate of androgen-independent prostate cancer cells following Fas receptor ligation.
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PMID:Activation of SAPK/JNK by camptothecin sensitizes androgen-independent prostate cancer cells to Fas-induced apoptosis. 1083 98

Sphingosine 1-phosphate (SPP) is associated with the regulation of apoptosis, although its role in neutrophil apoptosis remains poorly investigated. Here, we show that exogenous SPP antagonizes spontaneous and anti-Fas-induced apoptosis in neutrophils. Pre-treatment with pertussis toxin clearly reduced the apoptosis-inhibiting capacity of SPP. Consequently, we investigated the involvement of potential modulators of apoptosis that are activated downstream of Gi/G0-coupled receptors. Neither Akt activity nor change in basal activity of c-Jun N-terminal kinases was detected during apoptosis or after adding SPP. In contrast, there was a transient decrease in phosphorylation of both extracellular-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) during both spontaneous and anti-Fas-induced apoptosis. Although exogenous SPP reversed these reductions in kinase activity, experiments with inhibitors of ERK (PD98059) and p38 MAPK (SB203580) revealed that only SB203580 counteracted the effect of SPP. Thus, SPP counteracts neutrophil apoptosis via a Gi/G0 protein survival-signalling pathway that includes modulation of p38 MAPK activity.
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PMID:Sphingosine 1-phosphate antagonizes human neutrophil apoptosis via p38 mitogen-activated protein kinase. 1278 24