Suppression of Ras-stimulated transformation by the JNK signal transduction pathway
Authors
Kennedy, Norman J.Sluss, Hayla Karen
Jones, Stephen N.
Bar-Sagi, Dafna
Flavell, Richard A.
Davis, Roger J.
UMass Chan Affiliations
Department of Cell BiologyDepartment of Cancer Biology
Program in Molecular Medicine
Howard Hughes Medical Institute
Document Type
Journal ArticlePublication Date
2003-03-12Keywords
AnimalsCell 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
Metadata
Show full item recordAbstract
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.Source
Genes Dev. 2003 Mar 1;17(5):629-37. Link to article on publisher's site
DOI
10.1101/gad.1062903Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42216PubMed ID
12629045Related Resources
ae974a485f413a2113503eed53cd6c53
10.1101/gad.1062903