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Ubiquitin-Regulated Cell Proliferation and Cancer

  • Beatriz Pérez-Benavente
  • Alihamze Fathinajafabadi Nasresfahani
  • Rosa FarràsEmail author
Chapter
  • 227 Downloads
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Ubiquitin Eukaryotic ubiquitin conjugation E3 ligases Ubiquitin-dependent degradation Non-proteolytic ubiquitination Cell cycle Cancer 

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Beatriz Pérez-Benavente
    • 1
  • Alihamze Fathinajafabadi Nasresfahani
    • 1
  • Rosa Farràs
    • 1
    Email author
  1. 1.Oncogenic Signaling LaboratoryCentro de Investigación Príncipe FelipeValenciaSpain

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