Combined chemical and genetic approach to inhibit proteolysis by the proteasome.

Yeast
Galen A CollinsWilliam P Tansey

Abstract

Regulated protein destruction by the proteasome is crucial for the maintenance of normal cellular homeostasis. Much of our understanding of proteasome function stems from the use of drugs that inhibit its activity. Curiously, despite the importance of proteasomal proteolysis, previous studies have found that proliferation of the yeast Saccharomyces cerevisiae is relatively resistant to the effects of proteasome inhibitors such as MG132, even in the presence of mutations that increase inhibitor levels in cells. We reasoned that part of the resistance of S. cerevisiae to proteasome inhibitors stems from the fact that most proteasome inhibitors preferentially target the chymotryptic activity of the proteasome, and that the caspase-like and tryptic sites within the 20S core could compensate for proteasome function under these conditions. To test this hypothesis, we generated a strain of yeast in which the gene encoding the drug efflux pump Pdr5 is deleted, and the tryptic and caspase-like proteasome activities are inactivated by mutation. We find that this strain has dramatically increased sensitivity to the proteasome inhibitor MG132. Under these conditions, treatment of yeast with MG132 blocks progression through the cell cycle, ...Continue Reading

References

Dec 6, 1996·Science·R W KingM W Kirschner
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·C S Arendt, M Hochstrasser
Oct 6, 1997·The Journal of Biological Chemistry·W HeinemeyerD H Wolf
Mar 12, 1999·Annual Review of Medicine·A L Schwartz, A Ciechanover
Aug 31, 1999·Genes & Development·W Zachariae, K Nasmyth
Feb 7, 2002·Proceedings of the National Academy of Sciences of the United States of America·James A FlemingRonald K Blackman
Jul 26, 2002·Nature·Guri GiaeverMark Johnston
Mar 4, 2003·Nature Reviews. Molecular Cell Biology·Masafumi Muratani, William P Tansey
Oct 3, 2003·Nature Cell Biology·J Russell Lipford, Raymond J Deshaies
Dec 22, 2004·Molecular Cell·Nevan J KroganJack F Greenblatt
Nov 4, 2005·Nature·J Russell LipfordRaymond J Deshaies
Dec 13, 2005·Methods in Enzymology·Kyung Bo KimCraig M Crews
Jan 18, 2006·Annual Review of Medicine·Paul G RichardsonKenneth C Anderson
Mar 1, 2006·Current Opinion in Genetics & Development·Galen A Collins, William P Tansey
Dec 26, 2008·Journal of Peptide Science : an Official Publication of the European Peptide Society·Michael GrollLuis Moroder
Mar 11, 2009·DNA Repair·Anne Daulny, William P Tansey
Oct 9, 2009·Nature·Galen A CollinsWilliam P Tansey

❮ Previous
Next ❯

Citations

Apr 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Fuqiang Geng, William P Tansey
Mar 13, 2012·Annual Review of Biochemistry·Fuqiang GengWilliam P Tansey
May 2, 2017·Nature Chemical Biology·Linda LauingerAxel Diernfellner
Nov 26, 2014·Biomolecules·Tyler S McCann, William P Tansey
Sep 20, 2018·Molecular Biology of the Cell·Li Liu, David E Levin
Nov 8, 2017·The Journal of Biological Chemistry·Antonia A NemecRobert J Tomko
Apr 26, 2014·The Journal of Biological Chemistry·Alexander N PatanananSteven G Clarke
Jun 26, 2014·Expert Review of Proteomics·Tanya R Porras-Yakushi, Sonja Hess
May 27, 2016·The Journal of Biological Chemistry·Houqing YuAndreas Matouschek
Jan 7, 2017·Science·Jasvinder S AhujaG Valentin Börner
Oct 31, 2020·The Journal of Biological Chemistry·Adhish S WalvekarSunil Laxman
Jan 18, 2021·The Journal of Biological Chemistry·Adhish S WalvekarSunil Laxman
Mar 23, 2021·Human Molecular Genetics·Meredith PinkertonAntoni Barrientos
Jul 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Dimitra PanagakiJohanna L Höög
Jul 25, 2021·International Journal of Molecular Sciences·Manuel Sánchez López-BergesHubertus Haas
Nov 18, 2021··Mafalda Escobar-HenriquesIra Buntenbroich

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.