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MYC and RAF: Key Effectors in Cellular Signaling and Major Drivers in Human Cancer

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Viruses, Genes, and Cancer

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 407))

Abstract

The prototypes of the human MYC and RAF gene families are orthologs of animal proto-oncogenes that were originally identified as transduced alleles in the genomes of highly oncogenic retroviruses. MYC and RAF genes are now established as key regulatory elements in normal cellular physiology, but also as major cancer driver genes. Although the predominantly nuclear MYC proteins and the cytoplasmic RAF proteins have different biochemical functions, they are functionally linked in pivotal signaling cascades and circuits. The MYC protein is a transcription factor and together with its dimerization partner MAX holds a central position in a regulatory network of bHLH-LZ proteins. MYC regulates transcription conducted by all RNA polymerases and controls virtually the entire transcriptome. Fundamental cellular processes including distinct catabolic and anabolic branches of metabolism, cell cycle regulation, cell growth and proliferation, differentiation, stem cell regulation, and apoptosis are under MYC control. Deregulation of MYC expression by rearrangement or amplification of the MYC locus or by defects in kinase-mediated upstream signaling, accompanied by loss of apoptotic checkpoints, leads to tumorigenesis and is a hallmark of most human cancers. The critically controlled serine/threonine RAF kinases are central nodes of the cytoplasmic MAPK signaling cascade transducing converted extracellular signals to the nucleus for reshaping transcription factor controlled gene expression profiles. Specific mutations of RAF kinases, such as the prevalent BRAF(V600E) mutation in melanoma, or defects in upstream signaling or feedback loops cause decoupled kinase activities which lead to tumorigenesis. Different strategies for pharmacological interference with MYC- or RAF-induced tumorigenesis are being developed and several RAF kinase inhibitors are already in clinical use.

Dedication: This article is dedicated to Peter K. Vogt. His pioneering work has profound and sustained impact on the fields of virology and cancer genetics.

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Acknowledgements

We thank Gabriele Reiter for help with the preparation of the manuscript. Work by the authors has been supported by grants (P23652, P27606) from the Austrian Science Fund (FWF).

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  1. Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80–82, 6020, Innsbruck, Austria

    Eduard Stefan & Klaus Bister

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  1. Eduard Stefan
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  2. Klaus Bister
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Correspondence to Klaus Bister .

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  1. Emory Vaccine Center, Emory University, Atlanta, GA, USA

    Eric Hunter

  2. Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria

    Klaus Bister

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Stefan, E., Bister, K. (2017). MYC and RAF: Key Effectors in Cellular Signaling and Major Drivers in Human Cancer. In: Hunter, E., Bister, K. (eds) Viruses, Genes, and Cancer. Current Topics in Microbiology and Immunology, vol 407. Springer, Cham. https://doi.org/10.1007/82_2017_4

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