c-Jun N-Terminal Protein Kinase 1 (JNK1), but Not JNK2, Is Essential for Tumor Necrosis Factor Alpha-Induced c-Jun Kinase Activation and Apoptosis

Liu, Jing; Minemoto, Yuzuru; Lin, Anning

doi:10.1128/mcb.24.24.10844-10856.2004

Cited by 190 publications

(221 citation statements)

References 34 publications

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“…Overexpression of JNK1b1 increases resistance to vesicular stomatitis virus-induced cell death in 3T3 fibroblasts, whereas overexpression of JNK1a1 and JNK1b1 potentiates cisplatin-and doxorubicin-induced cell death in sarcoma cell lines (Han et al, 2002;Koyama et al, 2006). Previous studies have demonstrated a role for either JNK1 or JNK2 in TNFa-induced apoptosis (Dietrich et al, 2004;Liu et al, 2004). Our results show that the chief JNK isotype activated by DR4 and DR5 is JNK1.…”

Section: Jnk1a1 Has An Antiapoptotic Functionsupporting

confidence: 49%

Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines

et al. 2009

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Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis on binding to its receptors, death receptor 4 and 5 (DR4, DR5). TRAIL can also activate c-Jun N-terminal kinase (JNK) through the adaptor molecules, TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP). The role of JNK in TRAIL-induced tumour cell apoptosis is unclear. In this study, we demonstrate that JNK is activated by TRAIL in colon cancer cells. Inhibition of JNK with L-JNKI reduced rhTRAIL-induced cell death but enhanced cell death induced by selective activation of DR4 or DR5. This difference was unrelated to receptor internalisation or differential activation of c-Jun, but activation of different JNK isoforms. Our data demonstrate that JNK1, but not JNK2 is activated by rhTRAIL in the examined colon cancer cell lines. Although rhTRAIL activated both the long and short isoforms of JNK1, selective activation of DR4 or DR5 led to predominant activation of the short JNK1 isoforms (JNK1a1 and/or JNK1b1). Knockdown of JNK1a1 by shRNA enhanced apoptosis induced by TRAIL, agonistic DR4 or DR5 antibodies. On the other hand, knockdown of the long JNK1 isoforms (JNK1a2 and JNK1b2) had the opposite effect; it reduced TRAIL-induced cell death. These data indicate that the short JNK1 isoforms transmit an antiapoptotic signal, whereas the long isoforms (JNK1a2 or JNK1b2) act in a proapoptotic manner.

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Section: Jnk1a1 Has An Antiapoptotic Functionsupporting

confidence: 49%

Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines

et al. 2009

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“…3a). These are the JNK1a1 and JNK2a1 isoforms of JNK (Liu et al 2004). The increased amounts of activated JNK1/2 may reflect the increased levels of JNK1/2 in the treated cells, or may indicate that JNK1/2 are activated to a low level in SB203580 treated cells.…”

Section: Characterisation Of Stress Kinase Effector Pathwaysmentioning

confidence: 99%

Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of Ataxia Telangiectasia and Werner syndrome fibroblasts

Davis

Kipling

2008

Biogerontology

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The premature ageing Ataxia Telangiectasia (AT) and Werner syndromes (WS) are associated with accelerated cellular ageing. Young WS fibroblasts have an aged appearance and activated p38 MAP kinase, and treatment with the p38 inhibitor SB230580 extends their lifespan to within the normal range. SB203580 also extends the replicative lifespan of normal adult dermal fibroblasts, however, the effect is much reduced when compared to WS cells, suggesting that WS fibroblasts undergo a form of stress-induced premature senescence (SIPS). A small lifespan extension is seen in AT cells, which is not significant compared to normal fibroblasts, and the majority of young AT cells do not have an aged appearance and lack p38 activation, suggesting that the premature ageing does not result from SIPS. The lack of p38 activation is supported by the clinical manifestation, since AT is not associated with inflammatory disease, whereas WS individuals are predisposed to atherosclerosis, type II diabetes and osteoporosis, conditions known to be associated with p38 activation.

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“…Some of these differences were attributed to differential phosphorylation of the E3 ubiquitin ligase Itch by JNK1 and JNK2 isoforms (22). The preferential activation of Itch by JNK1 (23) may also explain the selective involvement of JNK1 rather than JNK2 in TNF-␣-induced cell death (24). Isolated JNK1 but not JNK2 deficiency results in reduced adiposity and increased insulin sensitivity in mouse models of obesity (10).…”

mentioning

confidence: 99%

Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance

Tuncman

Hirosumi

Solinas

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

323

262

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The c-Jun N-terminal kinases (JNKs) are key regulators of inflammation and interfere with insulin action in cultured cells and whole animals. Obesity increases total JNK activity, and JNK1, but not JNK2, deficiency results in reduced adiposity and improved insulin sensitivity. Interestingly, a higher-than-normal level of JNK activation is observed in Jnk2 ؊/؊ mice, particularly in the liver, indicating an interaction between the isoforms that might have masked the metabolic activity of JNK2 in isolated mutant mice. To address the role of the JNK2 isoform in metabolic homeostasis, we intercrossed Jnk1 ؊/؊ and Jnk2 ؊/؊ mice and examined body weight and glucose metabolism in the resulting mutant allele combinations. Among all of the viable genotypes examined, we observed only reduced body weight and increased insulin sensitivity in Jnk1 ؊/؊ and Jnk1 ؉/؊ Jnk2 ؊/؊ mice. These two groups of mice also exhibited reduced total JNK activity and cytokine expression in liver tissue compared with all other genotypes examined. These data indicate that the JNK2 isoform is also involved in metabolic regulation, but its function is not obvious when JNK1 is fully expressed because of regulatory crosstalk between the two isoforms.diabetes ͉ fatty liver ͉ metabolic syndrome ͉ inflammation ͉ stress

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c-Jun N-Terminal Protein Kinase 1 (JNK1), but Not JNK2, Is Essential for Tumor Necrosis Factor Alpha-Induced c-Jun Kinase Activation and Apoptosis

Cited by 190 publications

References 34 publications

Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines

Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines

Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of Ataxia Telangiectasia and Werner syndrome fibroblasts

Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance

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