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Ubiquitin, SUMO, and Nedd8 as Therapeutic Targets in Cancer

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Proteostasis and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1233))

Abstract

Ubiquitin defines a family of approximately 20 peptidic posttranslational modifiers collectively called the Ubiquitin-like (UbLs). They are conjugated to thousands of proteins, modifying their function and fate in many ways. Dysregulation of these modifications has been implicated in a variety of pathologies, in particular cancer. Ubiquitin, SUMO (-1 to -3), and Nedd8 are the best-characterized UbLs. They have been involved in the regulation of the activity and/or the stability of diverse components of various oncogenic or tumor suppressor pathways. Moreover, the dysregulation of enzymes responsible for their conjugation/deconjugation has also been associated with tumorigenesis and cancer resistance to therapies. The UbL system therefore constitutes an attractive target for developing novel anticancer therapeutic strategies. Here, we review the roles and dysregulations of Ubiquitin, SUMO, and Nedd8 pathways in tumorigenesis, as well as recent advances in the identification of small molecules targeting their conjugating machineries for potential application in the fight against cancer.

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Acknowledgments

We are grateful to all members of the “Oncogenesis and Immunotherapy” group of IGMM for support and fruitful discussions. Funding was provided by the CNRS, Ligue Nationale contre le Cancer (Programme Equipe Labellisée), INCA (ROSAML), Association Laurette Fugain (contract ALF-2017/02), the Fondation ARC (to PG), the Fédération Leucémie Espoir, The EpiGenMed Labex, and the ANR under the “Investissements d’avenir” programme (ANR-16-IDEX-0006).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Equipe Labellisée Ligue Contre le Cancer, IGMM, Univ Montpellier, CNRS, Montpellier, France

    Pierre Gâtel, Marc Piechaczyk & Guillaume Bossis

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  1. Pierre Gâtel
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  2. Marc Piechaczyk
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  3. Guillaume Bossis
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Correspondence to Guillaume Bossis .

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  1. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    Rosa Barrio

  2. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    James D. Sutherland

  3. Centre Pierre Potier, ITAV, Toulouse Cedex 1, France

    Manuel S. Rodriguez

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Gâtel, P., Piechaczyk, M., Bossis, G. (2020). Ubiquitin, SUMO, and Nedd8 as Therapeutic Targets in Cancer. In: Barrio, R., Sutherland, J., Rodriguez, M. (eds) Proteostasis and Disease . Advances in Experimental Medicine and Biology, vol 1233. Springer, Cham. https://doi.org/10.1007/978-3-030-38266-7_2

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