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Encyclopedia of Signaling Molecules pp 1562–1570Cite as

RAF-1 (C-RAF)

  • Reference work entry

  • 106 Accesses

Synonyms

C-Raf; c-Raf-1; Murine leukemia viral (v-raf-1) oncogene homolog 1 (3611-MSV); Murine sarcoma 3611 oncogene 1; Raf1; Raf-1; v-Raf; v-Raf-1 leukemia viral oncogene 1

Historical Background

Raf-1, also known as C-Raf-1 or C-Raf, was identified about 30 years ago as the oncogene (v-raf) in the murine sarcoma virus 3611 (3611-MSV) and, in parallel, in the naturally occurring avian retrovirus Mill Hill 2 (MH2). The gene was named after its enhancing effect on fibrosarcoma induction in newborn mice: Rapidly accelerated fibrosarcoma, or Raf. The sequences of the oncogenes, v-raf (derived from 3611-MSV) and v-mil (derived from MH2), were found to encode a serine/threonine protein kinase containing the catalytic, but not the N-terminal regulatory domain of the enzyme. This deletion rendered the protein constitutively active and was responsible for its transforming effect, making Raf the first oncogenic serine/threonine kinase discovered. A pseudogene (c-raf-2) and two paralogues of c-raf-1...

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References

  • Alavi AS, Acevedo L, Min W, Cheresh DA. Chemoresistance of endothelial cells induced by basic fibroblast growth factor depends on Raf-1-mediated inhibition of the proapoptotic kinase, ASK1. Cancer Res. 2007;67:2766–72.

    Article  PubMed  CAS  Google Scholar 

  • Arkenau HT, Kefford R, Long GV. Targeting BRAF for patients with melanoma. Br J Cancer. 2011;104:392–8.

    Article  PubMed  CAS  Google Scholar 

  • Baccarini M. Second nature: biological functions of the Raf-1 “kinase”. FEBS Lett. 2005;579:3271–7.

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Fujii K, Zhang L, Roberts T, Fu H. Raf-1 promotes cell survival by antagonizing apoptosis signal- regulating kinase 1 through a MEK-ERK independent mechanism. Proc Natl Acad Sci USA. 2001;98:7783–8.

    Article  PubMed  CAS  Google Scholar 

  • Cichowski K, Janne PA. Drug discovery: inhibitors that activate. Nature. 2010;464:358–9.

    Article  PubMed  CAS  Google Scholar 

  • Ehrenreiter K, Piazzolla D, Velamoor V, Sobczak I, Small JV, Takeda J, et al. Raf-1 regulates Rho signaling and cell migration. J Cell Biol. 2005;168:955–64.

    Article  PubMed  CAS  Google Scholar 

  • Ehrenreiter K, Kern F, Velamoor V, Meissl K, Galabova-Kovacs G, Sibilia M, et al. Raf-1 addiction in Ras-induced skin carcinogenesis. Cancer Cell. 2009;16:149–60.

    Article  PubMed  CAS  Google Scholar 

  • Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, et al. Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface. Biochemistry. 1995;34:6911–18.

    Article  PubMed  CAS  Google Scholar 

  • Galabova-Kovacs G, Kolbus A, Matzen D, Meissl K, Piazzolla D, Rubiolo C, et al. ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts. Cell Cycle. 2006;5:1514–18.

    Article  PubMed  CAS  Google Scholar 

  • Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature. 2010;464:431–5.

    Article  PubMed  CAS  Google Scholar 

  • Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell. 2010;140:209–21.

    Article  PubMed  CAS  Google Scholar 

  • Kern F, Niault T, Baccarini M. Ras and Raf pathways in epidermis development and carcinogenesis. Br J Cancer. 2011;104:229–34.

    Article  PubMed  CAS  Google Scholar 

  • King AJ, Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, et al. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res. 2006;66:11100–5.

    Article  PubMed  CAS  Google Scholar 

  • Kolch W. Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol. 2005;6:827–37.

    Article  PubMed  CAS  Google Scholar 

  • Maurer G, Tarkowski B, Baccarini M. Raf kinases in cancer – roles and therapeutic opportunities. Oncogene. 2011; in press.

    Google Scholar 

  • McKay MM, Morrison DK. Integrating signals from RTKs to ERK/MAPK. Oncogene. 2007;26:3113–21.

    Article  PubMed  CAS  Google Scholar 

  • Mercer K, Giblett S, Oakden A, Brown J, Marais R, Pritchard C. A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression. Oncogene. 2005;24:5207–17.

    Article  PubMed  CAS  Google Scholar 

  • Mott HR, Carpenter JW, Zhong S, Ghosh S, Bell RM, Campbell SL. The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site. Proc Natl Acad Sci USA. 1996;93:8312–17.

    Article  PubMed  CAS  Google Scholar 

  • Niault TS, Baccarini M. Targets of Raf in tumorigenesis. Carcinogenesis. 2010;31:1165–74.

    Article  PubMed  CAS  Google Scholar 

  • Niault T, Sobczak I, Meissl K, Weitsman G, Piazzolla D, Maurer G, et al. From autoinhibition to inhibition in trans: the Raf-1 regulatory domain inhibits Rok-alpha kinase activity. J Cell Biol. 2009;187:335–42.

    Article  PubMed  CAS  Google Scholar 

  • O’Neill E, Rushworth L, Baccarini M, Kolch W. Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science. 2004;306:2267–70.

    Article  PubMed  CAS  Google Scholar 

  • Pan D. The hippo signaling pathway in development and cancer. Dev Cell. 2010;19:491–505.

    Article  PubMed  CAS  Google Scholar 

  • Piazzolla D, Meissl K, Kucerova L, Rubiolo C, Baccarini M. Raf-1 sets the threshold of Fas sensitivity by modulating Rok-{alpha} signaling. J Cell Biol. 2005;171:1013–22.

    Article  PubMed  CAS  Google Scholar 

  • Romano D, Matallanas D, Weitsman G, Preisinger C, Ng T, Kolch W. Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt. Cancer Res. 2010;70:1195–203.

    Article  PubMed  CAS  Google Scholar 

  • Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nat Rev Mol Cell Biol. 2004;5:875–85.

    Article  PubMed  CAS  Google Scholar 

  • Wimmer R, Baccarini M. Partner exchange: protein-protein interactions in the Raf pathway. Trends Biochem Sci. 2010;35:660–8.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi O, Watanabe T, Nishida K, Kashiwase K, Higuchi Y, Takeda T, et al. Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis. J Clin Invest. 2004;114:937–43.

    PubMed  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank all the members of the Baccarini group for helpful discussions. Dr. Andrea Varga is supported by a FEBS long term fellowship. Work in the Baccarini lab is supported by funds of the Austrian National Research Fund (FWF), the Austrian Society for the Advancement of Research (FFG), the Obermann Foundation, and the European Community.

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Authors and Affiliations

  1. Department of Microbiology and Immunobiology, Center for Molecular Biology, University of Vienna, Max F. Perutz Laboratories, Dr. Bohr Gasse 9, A-1030, Vienna, Austria

    Dr. Andrea Varga & Dr. Manuela Baccarini

Authors
  1. Dr. Andrea Varga
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  2. Dr. Manuela Baccarini
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Corresponding author

Correspondence to Manuela Baccarini .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Varga, A., Baccarini, M. (2012). RAF-1 (C-RAF). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_591

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