Targeting the ubiquitin proteasome system in haematological malignancies

Lisa J Crawford, Alexandra E Irvine

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The ubiquitin proteasome system (UPS) plays a central role in cellular protein homeostasis through the targeted destruction of damaged/misfolded proteins and regulatory proteins that control critical cellular functions. The UPS comprises a sequential series of enzymatic activities to covalently attach ubiquitin to proteins to target them for degradation through the proteasome. Aberrancies within this system have been associated with transformation and tumourigenesis and thus, the UPS represents an attractive target for the development of anti-cancer therapies. The use of the first-in-class proteasome inhibitor, bortezomib, in the treatment of Plasma Cell Myeloma and Mantle Cell Lymphoma has validated the UPS as a therapeutic target. Following on its success, efforts are focused on the development of second-generation proteasome inhibitors and small molecule inhibitors of other components of the UPS. This review will provide an overview of the UPS and discuss current and novel therapies targeting the UPS.
Original languageEnglish
Pages (from-to)297-304
Number of pages8
JournalBlood Reviews
Volume27
Issue number6
Early online date19 Oct 2013
DOIs
Publication statusPublished - Nov 2013

Bibliographical note

© 2013 Elsevier Ltd. All rights reserved.

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