Role of c-Jun N-terminal kinase 1 (JNK1) in cell cycle checkpoint activated by the protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal

Tchou, Wen-Wei; Yie, Ting-An; Tan, Tse‐Hua; Rom, William N.; Tchou-Wong, Kam-Meng

doi:10.1038/sj.onc.1203195

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…MAP kinases are the most common signaling pathways known to mediate AP-1 function (27), and the blocking of MAP kinases leads to the inhibition of AP-1 transactivation and subsequent cell transformation (51)(52)(53)(54)(55)(56)(57). In the present study, however, we found no effect of EPA, DHA, or AA on TPA-or EGF-induced activation of JNKs, Erks, or p38 kinases, the three members of the MAP kinase family.…”

Section: Discussioncontrasting

confidence: 53%

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

Liu

Bibus

Bode

et al. 2001

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

102

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Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (3) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (6) fatty acids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fatty acids on tumorigenesis, we performed experiments to examine the effects of the 3 fatty acids EPA and DHA and of the 6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcription activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA-and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA-or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA-or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of 3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of 6 to 3 fatty acids may be a significant factor in mediating tumor development.

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Section: Discussioncontrasting

confidence: 53%

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

Liu

Bibus

Bode

et al. 2001

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

102

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“…1D and Table I). To further confirm this observation, we screened Calu-1 small lung carcinoma clones expressing a dominant-negative mutant, FLAGhuman JNK(APF), for changes in cell cycle distribution (20). FLAG-JNK(APF) expression was detected by Western blotting ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Cell Culture-Derivation of Calu-1 7-5, 8-5, and 8-30 clones has been described previously (20). Additional clones were derived by limiting…”

Section: Methodsmentioning

confidence: 99%

Inhibition of JNK2 Disrupts Anaphase and Produces Aneuploidy in Mammalian Cells

MacCorkle

Tan

2004

Journal of Biological Chemistry

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The JNK family members JNK1 and JNK2 regulate tumor growth and are essential for transformation by oncogenes such as constitutively activated Ras. The mechanisms downstream of JNK that regulate cell cycle progression and transformation are unclear. Here we show that inhibition of JNK2, but not JNK1, with either a dominant-negative mutant, a pharmacological inhibitor, or RNA interference caused an accumulation of mammalian cells with 4N DNA content. When observed by immunofluorescence, these cells progressed to metaphase without apparent defects in spindle formation or chromosome alignment to the metaphase plate, suggesting that the 4N accumulation is a result of postmetaphase defects. Consistent with this prediction, when JNK activity was suppressed, we observed defects in central spindle formation and chromosome segregation during anaphase. In contrast, cyclin-dependent kinase 1 activity, cyclin B1 protein, and Polo-like kinase 1 protein turnover remained intact when JNK was inhibited. In addition, continued inhibition of JNK activity did not block reentry into subsequent cell cycles but instead resulted in polyploidy. This evidence suggests that JNK2 functions in maintaining the genomic stability of mammalian cells by signaling that is independent of cyclin-dependent kinase 1/cyclin B1 down-regulation. JNK11 and JNK2 are members of the mitogen-activated protein kinase family, which also includes the prototypical family members extracellular signal-regulated kinase and p38. Mitogen-activated protein kinases are components of signal transduction pathways that connect extracellular stimuli to intracellular responses such as modulation of cell viability, cell cycle regulation, and gene expression (1-3). JNK1 and JNK2 are ubiquitously expressed and are generally considered to share redundant functions in apoptosis and transformation and differential functions in T cell differentiation (3-6). However, recent studies have shown that the stress-induced proapoptotic function previously attributed to both isoforms is actually a function specific to JNK1 (7,8). The function of JNK2, therefore, has become less clear. This suggests that JNK functions in transformation may also be isoform-specific and should be addressed in a way that differentiates between the contributions of JNK1 and JNK2.Ras-activating mutations have been identified in close to 30% of human cancers (9). Transformation by Ras requires JNK activity, which has made JNK an attractive target for cancer therapy (10 -12). Targeting JNK for cancer therapy is also supported by studies showing that JNK activity is elevated in human tumors and that loss of JNK function inhibits tumor growth in mice (13-16). The transforming mechanism downstream of JNK is not entirely clear, but it may work through the phosphorylation of c-Jun, which in turn regulates transcription of cell cycle regulators. In addition to this pathway, JNK may have a more direct function in cell cycle regulation. We have shown that JNK localizes to centrosomes and is active in this compartment from...

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“…The expression of c-Jun can be enhanced and prolonged by many stress stimuli such as ultraviolet, irradiation, hydrogen peroxide, tumor necrosis factor α and other apoptosis-triggering factors [45,46] . As mentioned above, VES-induced apoptosis rate was obviously decreased when human breast cancer cells were transfected with antisense c-Jun oligonucleotide or c-Jun mutant [18] .…”

Section: Discussionmentioning

confidence: 99%

Effect of vitamin E succinate on expression of TGF-β₁, c-Jun and JNK1 in human gastric cancer SGC-7901 cells

Liu²,

Zhao³

et al. 2001

WJG

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Role of c-Jun N-terminal kinase 1 (JNK1) in cell cycle checkpoint activated by the protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal

Cited by 12 publications

References 32 publications

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

Inhibition of JNK2 Disrupts Anaphase and Produces Aneuploidy in Mammalian Cells

Effect of vitamin E succinate on expression of TGF-β₁, c-Jun and JNK1 in human gastric cancer SGC-7901 cells

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Role of c-Jun N-terminal kinase 1 (JNK1) in cell cycle checkpoint activated by the protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal

Cited by 12 publications

References 32 publications

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

Inhibition of JNK2 Disrupts Anaphase and Produces Aneuploidy in Mammalian Cells

Effect of vitamin E succinate on expression of TGF-β1, c-Jun and JNK1 in human gastric cancer SGC-7901 cells

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Effect of vitamin E succinate on expression of TGF-β₁, c-Jun and JNK1 in human gastric cancer SGC-7901 cells