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Proteasome-associated deubiquitinases and cancer

Overview of attention for article published in Cancer and Metastasis Reviews, November 2017
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Title
Proteasome-associated deubiquitinases and cancer
Published in
Cancer and Metastasis Reviews, November 2017
DOI 10.1007/s10555-017-9697-6
Pubmed ID
Authors

Arjan Mofers, Paola Pellegrini, Stig Linder, Pádraig D’Arcy

Abstract

Maintenance of protein homeostasis is a crucial process for the normal functioning of the cell. The regulated degradation of proteins is primarily facilitated by the ubiquitin proteasome system (UPS), a system of selective tagging of proteins with ubiquitin followed by proteasome-mediated proteolysis. The UPS is highly dynamic consisting of both ubiquitination and deubiquitination steps that modulate protein stabilization and degradation. Deregulation of protein stability is a common feature in the development and progression of numerous cancer types. Simultaneously, the elevated protein synthesis rate of cancer cells and consequential accumulation of misfolded proteins drives UPS addiction, thus sensitizing them to UPS inhibitors. This sensitivity along with the potential of stabilizing pro-apoptotic signaling pathways makes the proteasome an attractive clinical target for the development of novel therapies. Targeting of the catalytic 20S subunit of the proteasome is already a clinically validated strategy in multiple myeloma and other cancers. Spurred on by this success, promising novel inhibitors of the UPS have entered development, targeting the 20S as well as regulatory 19S subunit and inhibitors of deubiquitinating and ubiquitin ligase enzymes. In this review, we outline the manner in which deregulation of the UPS can cause cancer to develop, current clinical application of proteasome inhibitors, and the (pre-)clinical development of novel inhibitors of the UPS.

Mendeley readers

The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 33%
Student > Bachelor 3 25%
Student > Ph. D. Student 2 17%
Researcher 2 17%
Other 1 8%
Other 0 0%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 58%
Pharmacology, Toxicology and Pharmaceutical Science 2 17%
Agricultural and Biological Sciences 2 17%
Medicine and Dentistry 1 8%