uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • 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
Elevation of Proteasomal Substrate Levels Sensitizes Cells to Apoptosis Induced by Inhibition of Proteasomal Deubiquitinases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
Show others and affiliations
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, e108839- p.Article in journal (Refereed) Published
Abstract [en]

Inhibitors of the catalytic activity of the 20S proteasome are cytotoxic to tumor cells and are currently in clinical use for treatment of multiple myeloma, whilst the deubiquitinase activity associated with the 19S regulatory subunit of the proteasome is also a valid target for anti-cancer drugs. The mechanisms underlying the therapeutic efficacy of these drugs and their selective toxicity towards cancer cells are not known. Here, we show that increasing the cellular levels of proteasome substrates using an inhibitor of Sec61-mediated protein translocation significantly increases the extent of apoptosis that is induced by inhibition of proteasomal deubiquitinase activity in both cancer derived and non-transformed cell lines. Our results suggest that increased generation of misfolded proteasome substrates may contribute to the mechanism(s) underlying the increased sensitivity of tumor cells to inhibitors of the ubiquitin-proteasome system.

Place, publisher, year, edition, pages
2014. Vol. 9, no 10, e108839- p.
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-240146DOI: 10.1371/journal.pone.0108839ISI: 000345743700036PubMedID: 25286379OAI: oai:DiVA.org:uu-240146DiVA: diva2:776621
Available from: 2015-01-07 Created: 2015-01-05 Last updated: 2017-12-05Bibliographically approved

Open Access in DiVA

fulltext(3409 kB)46 downloads
File information
File name FULLTEXT01.pdfFile size 3409 kBChecksum SHA-512
c665fd170c31172fed32d2af3ba0c1d938c48a475ce8e0c2bb969d57ac4833cab8bb71888e354f397e0d5d8e35f08d5d8202c9ce69381d45fbbb795dfae88d75
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Fryknäs, Mårten

Search in DiVA

By author/editor
Fryknäs, Mårten
By organisation
Cancer Pharmacology and Computational Medicine
In the same journal
PLoS ONE
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar
Total: 46 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: 396 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • 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