Suppression of Ras-stimulated transformation by the JNK signal transduction pathway
Norman J. Kennedy,Hayla Karen Sluss,Stephen N. Jones,Dafna Bar-Sagi,Richard A. Flavell,Roger J. Davis +5 more
TLDR
It is demonstrated that although JNK does play a role in transformation in vitro, JNK is not required for tumor development in vivo and this conclusion is consistent with the presence in human tumors of loss-of-function mutations in the JNK pathway.Abstract:
The c-Jun NH2-terminal kinase (JNK) phosphorylates and activates members of the activator protein-1 (AP-1) group of transcription factors and is implicated in oncogenic transformation. To examine the role of JNK, we investigated the effect of JNK deficiency on Ras-stimulated transformation. We demonstrate that although JNK does play a role in transformation in vitro, JNK is not required for tumor development in vivo. Importantly, the loss of JNK expression resulted in substantial increases in the number and growth of tumor nodules in vivo. Complementation assays demonstrated that this phenotype was caused by JNK deficiency. These data demonstrate that, in contrast to expectations, the normal function of JNK may be to suppress tumor development in vivo. This conclusion is consistent with the presence in human tumors of loss-of-function mutations in the JNK pathway.read more
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MAP kinase signalling pathways in cancer.
TL;DR: Recent findings and hypotheses on the role of MAPK pathways in cancer are discussed, with a focus on stress-activated pathways, which largely seem to counteract malignant transformation.
Journal ArticleDOI
AP-1: a double-edged sword in tumorigenesis
Robert Eferl,Erwin F. Wagner +1 more
TL;DR: This work focuses on the JUN and FOS proteins and aims to offer a new perspective on the molecular mechanisms that regulate the oncogenic and anti-oncogenic effects of AP-1 in tumour development.
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RAS oncogenes: weaving a tumorigenic web
TL;DR: This Review describes how RAS oncogenes exploit their extensive signalling reach to affect multiple cellular processes that drive tumorigenesis.
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Targeting JNK for therapeutic benefit: from junk to gold?
TL;DR: The evidence supporting the application of JNK inhibitors in inflammatory, vascular, neurodegenerative, metabolic and oncological diseases in humans is discussed, and the present status of drug discovery targeting JNK is described.
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scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila.
TL;DR: It is demonstrated, for the first time in Drosophila, that activated alleles of Ras and Notch can act as cooperating oncogenes in the development of epithelial tumors, and highlights the importance of epithelium polarity regulators in restraining onCogenes and preventing tumor formation.
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TL;DR: This review will focus on the JNK group of MAP kinases, which are characterized by the sequence TEY and the two stress-activatedMAP kinases: p38 with the sequence TGY, and the c-Jun NH2-terminal kinases (JNK) with the sequences TPY.