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Deubiquitinases in cancer: new functions and therapeutic options

Oncogene volume 31, pages 2373–2388 (2012)Cite this article

Abstract

Deubiquitinases (DUBs) have fundamental roles in the ubiquitin system through their ability to specifically deconjugate ubiquitin from targeted proteins. The human genome encodes at least 98 DUBs, which can be grouped into 6 families, reflecting the need for specificity in their function. The activity of these enzymes affects the turnover rate, activation, recycling and localization of multiple proteins, which in turn is essential for cell homeostasis, protein stability and a wide range of signaling pathways. Consistent with this, altered DUB function has been related to several diseases, including cancer. Thus, multiple DUBs have been classified as oncogenes or tumor suppressors because of their regulatory functions on the activity of other proteins involved in tumor development. Therefore, recent studies have focused on pharmacological intervention on DUB activity as a rationale to search for novel anticancer drugs. This strategy may benefit from our current knowledge of the physiological regulatory mechanisms of these enzymes and the fact that growth of several tumors depends on the normal activity of certain DUBs. Further understanding of these processes may provide answers to multiple remaining questions on DUB functions and lead to the development of DUB-targeting strategies to expand the repertoire of molecular therapies against cancer.

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Acknowledgements

Our study is supported by grants from Ministerio de Ciencia e Innovación-Spain, Fundación ‘M Botín’, PCTI-FICYT Asturias and European Union (FP7 MicroEnviMet). The Instituto Universitario de Oncología is supported by Obra Social Cajastur and Acción Transversal del Cáncer-RTICC.

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  1. J M Fraile and V Quesada: These authors contributed equally to this work.

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  1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain

    J M Fraile, V Quesada, D Rodríguez, J M P Freije & C López-Otín

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Fraile, J., Quesada, V., Rodríguez, D. et al. Deubiquitinases in cancer: new functions and therapeutic options. Oncogene 31, 2373–2388 (2012). https://doi.org/10.1038/onc.2011.443

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