Suppression of Ras-stimulated transformation by the JNK signal transduction pathway

UMMS Affiliation

Howard Hughes Medical Institute; Program in Molecular Medicine; Department of Cancer Biology; Department of Cell Biology

Publication Date


Document Type



Animals; Cell Line; Cell Transformation, Neoplastic; Fibroblasts; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Nude; Mitogen-Activated Protein Kinases; Neoplasms, Experimental; Signal Transduction; ras Proteins


Life Sciences | Medicine and Health Sciences


The c-Jun NH(2)-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.

DOI of Published Version



Genes Dev. 2003 Mar 1;17(5):629-37. Link to article on publisher's site

Journal/Book/Conference Title

Genes and development

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Link to Article in PubMed

PubMed ID