liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Deubiquitinase inhibition as a cancer therapeutic strategy
Department of Oncology and Pathology, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Oncology and Pathology, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Oncology and Pathology, Karolinska Institute, SE-171 76 Stockholm, Sweden.
2015 (English)In: Pharmacology and Therapeutics, ISSN 0163-7258, E-ISSN 1879-016X, Vol. 147, 32-54 p.Article, review/survey (Refereed) Published
Abstract [en]

The ubiquitin proteasome system (UPS) is the main system for controlled protein degradation and a key regulator of fundamental cellular processes. The dependency of cancer cells on a functioning UPS has made this an attractive target for development of drugs that show selectivity for tumor cells. Deubiquitinases (DUBs, ubiquitin isopeptidases) are components of the UPS that catalyze the removal of ubiquitin moieties from target proteins or polyubiquitin chains, resulting in altered signaling or changes in protein stability. A number of DUBs regulate processes associated with cell proliferation and apoptosis, and as such represent candidate targets for cancer therapeutics. The majority of DUBs are cysteine proteases and are likely to be more "druggable" than E3 ligases. Cysteine residues in the active sites of DUBs are expected to be reactive to various electrophiles. Various compounds containing α,β-unsaturated ketones have indeed been demonstrated to inhibit cellular DUB activity. Inhibition of proteasomal cysteine DUB enzymes (i.e. USP14 and UCHL5) can be predicted to be particularly cytotoxic to cancer cells as it leads to blocking of proteasome function and accumulation of proteasomal substrates. We here provide an overall review of DUBs relevant to cancer and of various small molecules which have been demonstrated to inhibit DUB activity.

Place, publisher, year, edition, pages
Elsevier, 2015. Vol. 147, 32-54 p.
National Category
Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:liu:diva-115756DOI: 10.1016/j.pharmthera.2014.11.002ISI: 000350189500004PubMedID: 25444757OAI: oai:DiVA.org:liu-115756DiVA: diva2:796320
Available from: 2015-03-18 Created: 2015-03-18 Last updated: 2017-12-04

Open Access in DiVA

fulltext(2010 kB)170 downloads
File information
File name FULLTEXT01.pdfFile size 2010 kBChecksum SHA-512
bb790a2c6e0f080b57e721b0f761b063ff71eb17aa66808ca38609d7e7c4951b7aeeeeb9f3d0e55dbf03bb6a60fe7f387e602dab90b6293ce66fa40d7f8cf642
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Wang, XinLinder, Stig

Search in DiVA

By author/editor
Wang, XinLinder, Stig
By organisation
Division of Drug ResearchFaculty of Health Sciences
In the same journal
Pharmacology and Therapeutics
Biomedical Laboratory Science/Technology

Search outside of DiVA

GoogleGoogle Scholar
Total: 170 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 214 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf