The c-Jun N-terminal Kinase 1 Activity Is Differentially Regulated by Specific Mechanisms during Apoptosis

Ham, Young-Mi; Choi, Joon-Seok; Chun, Kukjin; Joo, Sang-Hoon; Lee, Seung-Ki

doi:10.1074/jbc.m302997200

Cited by 38 publications

(41 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest that glucose deprivation and CDDP may induce apoptosis, at least partially, through the activation of JNK/SAPK and that the overexpression of ASNS may inhibit apoptosis through the suppression of this JNK/SAPK activation. Unlike our results, several reports showed that 5-FU and other anticancer drugs also induced apoptosis through the activation of JNK/SAPK (31)(32)(33)(34). Contrastingly, the genetic removal of SEK-1, an immediate upstream activator kinase of JNK, promoted apoptosis of hepatocytes and T cells (35,36), which proposes that JNK has a dual role in cell survival.…”

Section: Discussioncontrasting

confidence: 96%

Enhanced Expression of Asparagine Synthetase under Glucose-Deprived Conditions Protects Pancreatic Cancer Cells from Apoptosis Induced by Glucose Deprivation and Cisplatin

Cui

Darmanin²,

Natsuisaka

et al. 2007

Cancer Research

View full text Add to dashboard Cite

Although hypovasculature is an outstanding characteristic of pancreatic cancers, the tumor cells survive and proliferate under severe hypoxic, glucose-deprived conditions caused by low blood supply. It is well known that the hypoxia-inducible factor-1 pathway is essential for the survival of pancreatic cancer cells under hypoxic conditions. To discover how pancreatic cancer cells adapt to glucose deprivation as well as hypoxia, we sought glucose deprivation-inducible genes by means of a DNA microarray system. We identified 63 genes whose expression was enhanced under glucose-deprived conditions at >2-fold higher levels than under normal glucose conditions. Among these genes, asparagine synthetase (ASNS) was studied in detail. Although it is known to be associated with drug resistance in leukemia and oncogenesis triggered by mutated p53, its function is yet to be determined. In this study, we found that glucose deprivation induced the overexpression of ASNS through an AMP-activated protein kinaseindependent and activating transcription factor-4-dependent manner and that ASNS protects pancreatic cancer cells from apoptosis induced by glucose deprivation itself. ASNS overexpression also induced resistance to apoptosis triggered by cisplatin [cis-diammine-dichloroplatinum (CDDP)] and carboplatin, but not by 5-fluorouracil, paclitaxel, etoposide, or gemcitabine. We show that glucose deprivation induces the activation of c-jun NH 2 -terminal kinase (JNK)/stress-activated protein kinase (SAPK) in a mock transfectant but not in an ASNS transfectant. Consequently, an inhibitor of JNK/SAPK decreased the sensitivity of pancreatic cancer cells to apoptosis by glucose deprivation and CDDP. These results strongly suggest that ASNS is induced by glucose deprivation and may play a pivotal role in the survival of pancreatic cancer cells under glucose-deprived conditions. [Cancer Res 2007;67(7):3345-55]

show abstract

Section: Discussioncontrasting

confidence: 96%

Enhanced Expression of Asparagine Synthetase under Glucose-Deprived Conditions Protects Pancreatic Cancer Cells from Apoptosis Induced by Glucose Deprivation and Cisplatin

Cui

Darmanin²,

Natsuisaka

et al. 2007

Cancer Research

View full text Add to dashboard Cite

show abstract

“…The JNK pathway played a major role in the apoptotic effect of PKCyNuc because inhibition of JNK significantly decreased the apoptotic effect of the PKCy-Nuc. JNK has been implicated in the regulation of cell apoptosis in response to various stimuli (51,52) and has been shown to act downstream of PKCy (16,51,53,54). A role for the nuclear PKCy in the activation of JNK is further supported by recent studies that showed that the nuclear translocation of PKCy by etoposide preceded the activation of JNK in salivary gland acinar cells (30,53).…”

Section: Discussionmentioning

confidence: 93%

The Localization of Protein Kinase Cδ in Different Subcellular Sites Affects Its Proapoptotic and Antiapoptotic Functions and the Activation of Distinct Downstream Signaling Pathways

Gomel

Xiang

Finniss

et al. 2007

Molecular Cancer Research

View full text Add to dashboard Cite

Protein kinase CD (PKCD) regulates cell apoptosis and survival in diverse cellular systems. PKCD translocates to different subcellular sites in response to apoptotic stimuli; however, the role of its subcellular localization in its proapoptotic and antiapoptotic functions is just beginning to be understood. Here, we used a PKCD constitutively active mutant targeted to the cytosol, nucleus, mitochondria, and endoplasmic reticulum (ER) and examined whether the subcellular localization of PKCD affects its apoptotic and survival functions. PKCD-Cyto, PKCD-Mito, and PKCD-Nuc induced cell apoptosis, whereas no apoptosis was observed with the PKCD-ER. PKCD-Cyto and PKCD-Mito underwent cleavage, whereas no cleavage was observed in the PKCD-Nuc and PKCD-ER. Similarly, caspase-3 activity was increased in cells overexpressing PKCD-Cyto and PKCD-Mito. In contrast to the apoptotic effects of the PKCD-Cyto, PKCD-Mito, and PKCD-Nuc, the PKCD-ER protected the cells from tumor necrosis factor -related apoptosis-inducing ligand -induced and etoposideinduced apoptosis. Moreover, overexpression of a PKCD kinase-dead mutant targeted to the ER abrogated the protective effect of the endogenous PKCD and increased tumor necrosis factor -related apoptosis-inducing ligand -induced apoptosis. The localization of PKCD differentially affected the activation of downstream signaling pathways. PKCD-Cyto increased the phosphorylation of p38 and decreased the phosphorylation of AKT and the expression of X-linked inhibitor of apoptosis protein, whereas PKCD-Nuc increased c-Jun NH 2 -terminal kinase phosphorylation. Moreover, p38 phosphorylation and the decrease in X-linked inhibitor of apoptosis protein expression played a role in the apoptotic effect of PKCD-Cyto, whereas c-Jun NH 2 -terminal kinase activation mediated the apoptotic effect of PKCD-Nuc. Our results indicate that the subcellular localization of PKCD plays important roles in its proapoptotic and antiapoptotic functions and in the activation of downstream signaling pathways.

show abstract

“…(Fig. 6), and both have been implicated in mediating apoptosis in response to paclitaxel treatment (28,29,38,39). We have reported previously that BRCA1 sensitizes breast cancer cells to paclitaxelinduced apoptosis (21).…”

Section: Discussionmentioning

confidence: 93%

BRCA1 Interacts with and Is Required for Paclitaxel-Induced Activation of Mitogen-Activated Protein Kinase Kinase Kinase 3

Gilmore¹,

McCabe²,

Quinn³

et al. 2004

Cancer Research

View full text Add to dashboard Cite

BRCA1 has been implicated in a number of cellular processes, including transcriptional regulation, DNA damage repair, cell cycle arrest, and apoptosis. We identified mitogen-activated protein kinase (MAPK) kinase kinase 3 (MEKK3), an upstream regulator of the c-Jun NH 2 -terminal kinase/stress-activated protein kinase and p38/MAPK pathways, as a novel BRCA1-interacting protein in a yeast two-hybrid screen and confirmed the interaction by coimmunoprecipitation in mammalian cells. Deletion mapping demonstrated that amino acids 1611-1863 are required to mediate the interaction with MEKK3 in yeast. BRCA1 disease-associated mutations abrogated the interaction in yeast, and BRCA1 failed to interact with MEKK3 in BRCA1 mutant HCC1937 breast cancer cells. We demonstrate that small interfering RNA-based inhibition of endogenous BRCA1 reduces MEKK3 kinase activity and conversely that inducible expression of BRCA1 activates MEKK3 and p38/MAPK. Finally, we demonstrate using complementary approaches that BRCA1 is required for paclitaxel-induced activation of MEKK3. These data indicate that BRCA1 is a key regulator of the paclitaxel-induced stress response pathway and suggest that the ability of BRCA1 to associate with, and mediate the activation of, MEKK3 represents a potential mechanism through which this pathway is regulated.

show abstract

The c-Jun N-terminal Kinase 1 Activity Is Differentially Regulated by Specific Mechanisms during Apoptosis

Cited by 38 publications

References 35 publications

Enhanced Expression of Asparagine Synthetase under Glucose-Deprived Conditions Protects Pancreatic Cancer Cells from Apoptosis Induced by Glucose Deprivation and Cisplatin

Enhanced Expression of Asparagine Synthetase under Glucose-Deprived Conditions Protects Pancreatic Cancer Cells from Apoptosis Induced by Glucose Deprivation and Cisplatin

The Localization of Protein Kinase Cδ in Different Subcellular Sites Affects Its Proapoptotic and Antiapoptotic Functions and the Activation of Distinct Downstream Signaling Pathways

BRCA1 Interacts with and Is Required for Paclitaxel-Induced Activation of Mitogen-Activated Protein Kinase Kinase Kinase 3

Contact Info

Product

Resources

About