Activation of c-Jun N-terminal Kinase Antagonizes an Anti-apoptotic Action of Bcl-2

Park, Jihyun; Kim, In Jung; Oh, Young Jun; Lee, Ko Woon; Han, Pyung Lim; Choi, Eui Ju

doi:10.1074/jbc.272.27.16725

Cited by 112 publications

(87 citation statements)

References 25 publications

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“…Interestingly, it has recently been shown that overexpression of SAPK/JNK antagonized the anti-apoptotic effect of Bcl-2, presumably due to sustained activation of SAPK/JNK (Park et al, 1997). Pro-apoptotic Bcl-2 family members, such as Bax, can antagonize the effects exerted by the anti-apoptotic members.…”

Section: Discussionmentioning

confidence: 99%

Activation of SAPK/JNK by camptothecin sensitizes androgen-independent prostate cancer cells to Fas-induced apoptosis

2000

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SummaryWe 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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Section: Discussionmentioning

confidence: 99%

Activation of SAPK/JNK by camptothecin sensitizes androgen-independent prostate cancer cells to Fas-induced apoptosis

2000

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“…Actually, JNK induces the expression of BH3-only proteins: Hrk and Bim (Harris and Johnson, 2001). Jun N-terminal kinase also phosphorylates Bcl-2 family members and promotes pro-apoptotic Bax activity (Kim et al, 2006), and inhibits various anti-apoptotic Bcl-2 family members, including Bcl-2, Bcl-x L and Mcl-1 (Ito et al, 1997;Park et al, 1997). In addition, JNK indirectly determines the activation of Bax through its regulation of 14-3-3 (Tsuruta et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Involvement of JNK in the regulation of autophagic cell death

et al. 2010

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Programmed cell death is a crucial process in the normal development and physiology of metazoans, and it can be divided into several categories that include type I death (apoptosis) and type II death (autophagic cell death). The Bcl-2 family proteins are well-characterized regulators of apoptosis, among which multidomain pro-apoptotic members (such as Bax and Bak) function as a mitochondrial gateway at which various apoptotic signals converge. Although embryonic fibroblasts from Bax/Bak doubleknockout (DKO) mice are resistant to apoptosis, we have previously reported that these cells still die by autophagy in response to various death stimuli. In this study, we found that jun N-terminal kinase (JNK) was activated in etoposide-and staurosporine-treated, but not serumstarved, Bax/Bak DKO cells, and that autophagic cell death was suppressed by the addition of a JNK inhibitor and by a dominant-negative mutant of JNK. Studies with sek1À/À cells revealed that disruption of JNK prevented the induction of autophagic cell death. Coactivation of JNK and autophagy induced autophagic cell death. Activation of JNK occurred downstream of the induction of autophagy, and was dependent on the autophagic process. These results indicate that JNK activation is crucial for the autophagic death of Bax/ Bak DKO cells.

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“…35 Correspondingly, activation of the JNK/SAPK pathway in combination with a repressed growth factor activated ERK-cascade has been shown to be required for apoptosis and a balance between JNK/SAPK and ERK has been found to be critical in affecting the apoptotic outcome. 30 In addition, JNK/SAPK activity may also occur independently of death receptor triggering as described in response to cellular stress.…”

Section: Discussionmentioning

confidence: 99%

JNK/SAPK activity contributes to TRAIL-induced apoptosis

et al. 1999

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We report here that JNK/SAPKs are activated by TRAIL in parallel to induction of apoptosis in human T and B cell lines. Death signaling as well as JNK/SAPK activation by TRAIL in these cells is FADD-and caspase-dependent since dominantnegative FADD or the caspase inhibitor zVAD prevented both, apoptosis and JNK/SAPK activity. JNK/SAPK activity in response to triggering of CD95 by an agonistic antibody (aAPO-1) was also diminished by dominant-negative FADD or zVAD. Correspondingly, a cell line resistant to aAPO-1-induced death exhibited crossresistance to TRAIL-induced apoptosis and did not upregulate JNK/SAPK activity in response to TRAIL or aAPO-1. Inhibition of JNK/SAPK activity, by stably transfecting cells with a dominant-negative JNKK-MKK4 construct, reduced apoptosis in response to TRAIL or aAPO-1. Therefore, activation of JNK/SAPKs by TRAIL or aAPO-1 occurs downstream of FADD and caspases and contributes to apoptosis in human lymphoid cell lines.

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Activation of c-Jun N-terminal Kinase Antagonizes an Anti-apoptotic Action of Bcl-2

Cited by 112 publications

References 25 publications

Activation of SAPK/JNK by camptothecin sensitizes androgen-independent prostate cancer cells to Fas-induced apoptosis

Activation of SAPK/JNK by camptothecin sensitizes androgen-independent prostate cancer cells to Fas-induced apoptosis

Involvement of JNK in the regulation of autophagic cell death

JNK/SAPK activity contributes to TRAIL-induced apoptosis

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