Targets of Raf in tumorigenesis.
Some 25 years ago, Raf was discovered as the transforming principle shared by a murine sarcoma and an avian carcinoma virus. Thus, Raf and tumorigenesis have been connected from the very beginning. Ten years later, the work of many groups instated Raf as the link between Ras, the oncogene most frequently mutated in human cancers, and the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK/ERK) module, which with its manifold substrates can contribute to different aspects of carcinogenesis. Finally, the discovery of activating B-Raf mutations in a subset of human cancers, notably melanomas, conclusively established Raf as a major player in tumor development. Recent studies in animal models now show that endogenous C-Raf is essential for the development and maintenance of Ras-induced epidermal tumors. Surprisingly, the role of C-Raf in this case is not that of an mitogen-activated protein kinase activator, but rather that of an endogenous inhibitor of Rho signaling, expanding the range of tumor-related Raf targets. This review focuses on old and new targets of Raf in tumorigenesis.
Niault
Théodora S
TS
Center for Molecular Biology, Max F Perutz Laboratories, University of Vienna, Doktor-Bohr-Gasse 9, 1030 Vienna, Austria.
Baccarini
Manuela
M
D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D011905:Genes, ras; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D009369:Neoplasms / Q000209:etiology*; D048493:Proto-Oncogene Proteins B-raf / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D015398:Signal Transduction; D048490:raf Kinases / Q000502:physiology*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases