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Protein Complex Hierarchy and Translocation Gene Products

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Chromosomal Translocations and Genome Rearrangements in Cancer

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Abstract

Disease-causing chromosomal translocations tend to cause the up-regulated expression of proteins, or result in fusion proteins with altered functionality. Four sets of chromosomal translocations are presented as case studies to illustrate how the protein products of chromosomal translocations disrupt normal cellular processes through a range of different mechanisms. For translocations affecting LMO2 and MYC expression, alterations to transcriptional regulation ultimately cause disease. In the case of the Philadelphia Chromosome, BCR-ABL1 disrupts cell signalling and cell cycle regulation by generating an always active form of the ABL1 tyrosine kinase. Upregulation of BCL2 blocks apoptosis. In each case the molecular basis of activity, and strategies for inhibition by directly targeting the disease causing proteins are summarized.

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Authors and Affiliations

  1. School of Molecular Bioscience, The University of Sydney, Sydney, Australia

    Jacqueline M. Matthews

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  1. Jacqueline M. Matthews
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Correspondence to Jacqueline M. Matthews .

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Editors and Affiliations

  1. Dept. of Medicine, Section of Hematol./Oncol., University of Chicago, CHICAGO, Illinois, USA

    Janet D. Rowley

  2. Section of Hematology/Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA

    Michelle M. Le Beau

  3. Weatherall Inst. of Molecular Medicine MRC Molecular Haematology Unit, University of Oxford, Oxford, United Kingdom

    Terence H. Rabbitts

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Matthews, J.M. (2015). Protein Complex Hierarchy and Translocation Gene Products. In: Rowley, J., Le Beau, M., Rabbitts, T. (eds) Chromosomal Translocations and Genome Rearrangements in Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-19983-2_21

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