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Targeting the ubiquitin system in cancer therapy

Nature volume 458, pages 438–444 (2009)Cite this article

Abstract

The ubiquitin system is a network of proteins dedicated to the ubiquitylation of cellular targets and the subsequent control of numerous cellular functions. The deregulation of components of this elaborate network leads to human pathogenesis, including the development of many types of tumour. Alterations in the ubiquitin system that occur during the initiation and progression of cancer are now being uncovered, and this knowledge is starting to be exploited for both molecular diagnostics and the development of novel strategies to combat cancer.

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Figure 1: The ubiquitin system offers several possibilities for therapeutic intervention.
Figure 2: Different strategies to target inhibitors of apopotosis (IAPs) in cancer.
Figure 3: Non-degradative ubiquitin modifications have a role in DNA repair.
Figure 4: Targeting the ubiquitin system in the nucleus.

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Acknowledgements

We thank A. Ciechanover, R. Deshaies, M. Pagano, K. Rajalingam, D. Vucic and members of the Dikic laboratory for critical reading of the manuscript. We apologize to those investigators whose contributions are not described here because of space limitations. D.H. is supported by a European Molecular Biology Organization (EMBO) long-term fellowship. I.D. acknowledges support from the German Research Foundation (DFG) and the Cluster of Excellence 'Macromolecular Complexes' (Goethe University Frankfurt).

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Authors and Affiliations

  1. Division of Medical Biochemistry, Innsbruck Medical University, Biocenter, Fritz-Pregl-Strasse 3, Innsbruck, 6020, Austria

    Daniela Hoeller

  2. Institute of Biochemistry II and Cluster of Excellence 'Macromolecular Complexes', Goethe University, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany

    Ivan Dikic

  3. Tumor Biology Program, Mediterranean Institute for Life Sciences, Split, 21000, Croatia

    Ivan Dikic

  4. Department of Immunology, School of Medicine, University of Split, Soltanska 2, Split, 21000, Croatia

    Ivan Dikic

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Correspondence should be addressed to I.D (dikic@biochem2.uni-frankfurt.de).

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Hoeller, D., Dikic, I. Targeting the ubiquitin system in cancer therapy. Nature 458, 438–444 (2009). https://doi.org/10.1038/nature07960

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