The Role of c-Jun N-terminal Kinase (JNK) in Apoptosis Induced by Ultraviolet C and γ Radiation

Chen, Yirong; Wang, Xiaoping; Templeton, Dennis J.; Davis, Roger J.; Tan, Tse‐Hua

doi:10.1074/jbc.271.50.31929

Cited by 822 publications

(649 citation statements)

References 42 publications

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“…For example, though it has been demonstrated that inhibition of JNK signaling does not block Fasmediated killing in Jurkat T cells (Chen et al, 1996b;Lenczowski et al, 1997), it was found that Fasmediated apoptosis in neuroblastoma cells requires the JNK pathway (Goillot et al, 1997). Similarly, and in contrast to the evidence provided by the jnk3 knockout, data from the TRAF2 knockout mouse suggest that TRAF2 signaling of JNK activation protects against TNF-induced apoptosis (Yeh et al, 1997).…”

Section: Jnks and Apoptosismentioning

confidence: 99%

“…Adaptor proteins eventually bind a proximal caspase, eliciting autoactivation, thereby connecting receptor signaling by TNF and Fas to the apoptotic machinery (SchulzeOstho et al, 1998). Ceramide generation has been molecularly ordered downstream of the death adaptor proteins TRADD and FADD/MORT1 and upstream of e ector caspases (Chinnaiyan et al, 1996). TRADD and FADD appear to link speci®cally to the acidic form of SMase (Schwandner et al, 1998).…”

Section: Ceramide Generation Upstream Of Caspasesmentioning

confidence: 99%

“…The evidence that the JNK pathway is pro-apoptotic derives from studies that show that these kinases are activated rapidly in cells destined to undergo an apoptotic response, that their overexpression results in apoptosis in some cells, that anti-sense inhibition or the use of dominant negative constructs attenuates the apoptotic response, and in a recent publication by the use of a knock-out mouse Brenner et al, 1997;Butter®eld et al, 1997;Cardone et al, 1997;Chen et al, 1996a,b;Chuang et al, 1997;Frisch et al, 1996;Goillot et al, 1997;Seimiya et al, 1997;Verheij et al, 1996;Xia et al, 1995;Yang et al, 1997a;Zanke et al, 1996). In the latter studies, in mice de®cient in JNK3, which is restricted to the brain, there was a reduction in seizure activity and hippocampal apoptosis in response to the excitotoxic glutamate-receptor agonist kainic acid (Yang et al, 1997a).…”

Section: Jnks and Apoptosismentioning

confidence: 99%

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Stress signals for apoptosis: ceramide and c-Jun kinase

1998

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Section: Jnks and Apoptosismentioning

confidence: 99%

Section: Ceramide Generation Upstream Of Caspasesmentioning

confidence: 99%

Section: Jnks and Apoptosismentioning

confidence: 99%

See 1 more Smart Citation

Stress signals for apoptosis: ceramide and c-Jun kinase

1998

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“…Like p38, JNK was shown to elicit either an anti-or a pro-apoptotic signal, depending on the type of cells and damage. For example, JNK can elicit a pro-apoptotic signal via upregulation of Fas ligand expression (Faris et al, 1998a,b) in response to various stimuli, including cisplatin (Sanchez-Perez and Perona, 1999) and UV-irradiation (Chen et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

p38 protects human melanoma cells from UV-induced apoptosis through down-regulation of NF-κB activity and Fas expression

2000

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Identifying mechanisms that underlie the resistance of human melanoma to radiation and chemotherapy is expected to assist in developing new strategies for the treatment of this tumor type. We recently demonstrated that through up-regulation of TNFa, ATF2 increases the resistance of late stage melanoma cells to apoptosis induced by UV-irradiation. In elucidating the role of ATF2 kinases, we now demonstrate that ASK1/MKK6/ p38 elicits suppression of Fas expression. ASK1/p38 downregulates the expression of a Fas via NF-kB/SP1 site on the Fas promoter. Deletion or mutation of NFkB/SP1 within the Fas promoter abrogates p38 e ect. ASK1/p38 silences the Fas promoter by inhibition of IkBa phosphorylation ± thereby limiting NF-kB activity. Forced expression of a dominant negative form of p38 (p38-ASP) or treatment with p38 pharmacological inhibitor, SB203580, increases NF-kB activity, Fas expression and the levels of UVC-induced apoptosis in late stage melanoma cells. Inhibition of p38 activity also restored NF-kB activity and Fas expression in earlyphase melanoma cells, suggesting that p38 elicited suppression of Fas expression is not restricted to late phase melanoma. Identifying p38-mediated down-regulation of Fas expression illustrates a novel regulatory pathway by which ASK1/MKK6/p38 alters the degree and nature of the UV-induced apoptosis of melanoma cells.

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“…JNK activation follows recruitment of Daxx, rather than FADD, to the Fas death domain (Yang et al, 1997;Chang et al, 1998) and a dominant negative form of FADD does not block JNK activation by Fas stimulation (Wajant et al, 1998). JNK activation has also been demonstrated during apoptosis in response to irradiation, heat shock, cisplatin, NGF removal, and TNF or ceramide treatment (Chen et al, 1996;Zanke et al, 1996;Xia et al, 1995;Verheij et al, 1996;Cuvillier et al, 1996;Ichijo et al, 1997;Shirakabe et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

JNK activation is not required for Fas-mediated apoptosis

et al. 1999

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Fas ligation in the presence of cycloheximide induced Jun N-terminal kinase 1 (JNK1) and JNK2 phosphorylation, caspase activation and cell death in the IL-3-dependent cell line BAF3. Fas-mediated apoptosis was prevented by expression of dominant negative FADD but not inhibited by IL-3. To investigate the role of JNK activation in this process, we examined cells overexpressing a JNK-speci®c phosphatase M3/6. M3/6 prevented Fas stimulation of JNK, but did not a ect Fas-mediated caspase activation or cell death, demonstrating that JNK activation is not required for these processes.

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The Role of c-Jun N-terminal Kinase (JNK) in Apoptosis Induced by Ultraviolet C and γ Radiation

Cited by 822 publications

References 42 publications

Stress signals for apoptosis: ceramide and c-Jun kinase

Stress signals for apoptosis: ceramide and c-Jun kinase

p38 protects human melanoma cells from UV-induced apoptosis through down-regulation of NF-κB activity and Fas expression

JNK activation is not required for Fas-mediated apoptosis

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