Inhibition of proteasome deubiquitinase activity: a strategy to overcome resistance to conventional proteasome inhibitors?

Inhibition of proteasome deubiquitinase activity : a strategy to overcome resistance to conventional proteasome inhibitors?

Selvaraju, Karthik (author): Linköpings universitet,Institutionen för medicin och hälsa,Medicinska fakulteten

Mazurkiewicz, Magdalena (author): Karolinska Institutet,Karolinska Institute, Sweden

Wang, Xin (author): Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten

Gullbo, Joachim (author): Uppsala universitet,Cancerfarmakologi och beräkningsmedicin,Experimentell och klinisk onkologi,Uppsala University, Sweden

Linder, Stig (author): Linköpings universitet,Karolinska Institutet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Karolinska Institute, Sweden

D´arcy, Padraig (author): Linköpings universitet,Karolinska Institutet,Avdelningen för läkemedelsforskning,Medicinska fakulteten

(creator_code:org_t)

Elsevier BV, 2015
2015
English.
In: Drug resistance updates. - : Elsevier BV. - 1368-7646 .- 1532-2084. ; 21-22, s. 20-29

Related links:: http://liu.diva-port...; show more...; https://liu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; https://urn.kb.se/re...; show less...

Abstract Subject headings

Although more traditionally associated with degradation and maintenance of protein homeostasis, the ubiquitin-proteasome system (UPS) has emerged as a critical component in the regulation of cancer cell growth and survival. The development of inhibitors that block the proteolytic activities of the proteasome have highlighted its suitability as a bona fide anti-cancer drug target. However, key determinants including the development of drug resistance and dose-limiting toxicity call for the identification of alternative components of the UPS for novel drug targeting. Recently the deubiquitinases (DUBS), a diverse family of enzymes that catalyze ubiquitin removal, have attracted significant interest as targets for the development of next generation UPS inhibitors. In particular, pharmacological inhibition of the proteasomal cysteine DUBs (i.e., USP14 and UCHL5) has been shown to be particularly cytotoxic to cancer cells and inhibit tumour growth in several in vivo models. In the current review we focus on the modes of action of proteasome DUB inhibitors and discus the potential of DUB inhibitors to circumvent acquired drug resistance and provide a therapeutic option for the treatment of cancer.

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)

By the author/editor: Selvaraju, Karth ...; Mazurkiewicz, Ma ...; Wang, Xin; Gullbo, Joachim; Linder, Stig; D´arcy, Padraig

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

By the university: Uppsala University; Karolinska Institutet; Linköping University

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.