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Ubiquitin-Regulated Cell Proliferation and Cancer

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Proteostasis and Disease

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

Abstract

Ubiquitin ligases (E3) play a crucial role in the regulation of different cellular processes such as proliferation and differentiation via recognition, interaction, and ubiquitination of key cellular proteins in a spatial and temporal regulated manner. The type of ubiquitin chain formed determines the fate of the substrates. The ubiquitinated substrates can be degraded by the proteasome, display altered subcellular localization, or can suffer modifications on their interaction with functional protein complexes. Deregulation of E3 activities is frequently found in various human pathologies, including cancer. The illegitimated or accelerated degradation of oncosuppressive proteins or, inversely, the abnormally high accumulation of oncoproteins, contributes to cell proliferation and transformation. Anomalies in protein abundance may be related to mutations that alter the direct or indirect recognition of proteins by the E3 enzymes or alterations in the level of expression or activity of ubiquitin ligases. Through a few examples, we illustrate here the complexity and diversity of the molecular mechanisms related to protein ubiquitination involved in cell cycle regulation. We will discuss the role of ubiquitin-dependent degradation mediated by the proteasome, the role of non-proteolytic ubiquitination during cell cycle progression, and the consequences of this deregulation on cellular transformation. Finally, we will highlight the novel opportunities that arise from these studies for therapeutic intervention.

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  1. Authors “Beatriz Pérez-Benavente” and “Alihamze Fathinajafabadi Nasresfahani” contributed equally for this chapter.

Authors and Affiliations

  1. Oncogenic Signaling Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain

    Beatriz Pérez-Benavente, Alihamze Fathinajafabadi Nasresfahani & Rosa Farràs

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  1. Beatriz Pérez-Benavente
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  3. Rosa Farràs
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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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Pérez-Benavente, B., Nasresfahani, A.F., Farràs, R. (2020). Ubiquitin-Regulated Cell Proliferation and 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_1

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