Role of JNK in tumor development.
The c-Jun NH2-terminal kinase (JNK) is implicated in oncogenic transformation. However, studies of the effect of Jnk gene disruption on Ras-induced transformation of murine fibroblasts indicate that JNK may act as a suppressor of Ras transformation and that the JNK signaling pathway contributes to the apoptotic elimination of transformed cells in vivo. The conclusion that JNK can act as a tumor suppressor is consistent with the presence of loss-of-function mutations in JNK pathway components (Jnk3 and Mkk4) in human tumors. Nevertheless, JNK can also contribute to the proliferation and survival responses of some tumors. A key question that remains unresolved concerns the genetic and mechanistic basis for these different roles of JNK in tumors. Indeed, an understanding of this question will be required for the rational use of small molecule inhibitors of JNK for tumor therapy.
Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Norman J
NJ
Kennedy
Roger J
RJ
Davis
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005057:Eukaryotic Cells / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins