Targeting the ubiquitin proteasome system in haematological malignancies.

Autor: Crawford LJ; Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, United Kingdom., Irvine AE
Jazyk: angličtina
Zdroj: Blood reviews [Blood Rev] 2013 Nov; Vol. 27 (6), pp. 297-304. Date of Electronic Publication: 2013 Oct 19.
DOI: 10.1016/j.blre.2013.10.002
Abstrakt: 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.
(© 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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