Pyrrolidine dithiocarbamate and zinc inhibit proteasome-dependent proteolysis

Experimental Cell Research
Insook KimYoung Soo Ahn

Abstract

Proteasomes play important roles in a variety of cellular processes such as cell cycle progression, signal transduction and immune responses. Proteasome activity is important in maintaining rapid turnover of short-lived proteins, as well as preventing accumulation of misfolded or damaged proteins. Alteration in ubiquitin-proteasome function may be detrimental to its crucial role in maintaining cellular homeostasis. Here, we have found that treatment of pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, resulted in the accumulation of several proteasome substrates including p53 and p21 in HeLa cells. The PDTC effect was due to an extended half-life of these proteins through the mobilization of zinc. PDTC and/or zinc also increased fluorescence intensity of Ub(G76V)-GFP fusion protein that is degraded rapidly by the ubiquitin-proteasome system. Treatment of cells with zinc induced formation of ubiquitinated inclusions in the centrosome, a histological marker of proteasome inhibition. Western blotting showed zinc-induced increase in laddering bands of polyubiquitin-conjugated proteins. In vitro study, zinc inhibited the ubiquitin-independent proteasomal degradations of p21 and alpha-synuclein. These results suggest that zinc ma...Continue Reading

References

May 1, 1992·The Journal of Experimental Medicine·R SchreckP A Baeuerle
Mar 24, 1990·Lancet·E C ReisingerM Dietrich
Jul 1, 1994·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·P D ZalewskiI Mahadevan
Oct 14, 1996·Biochemical and Biophysical Research Communications·M V BlagosklonnyW S el-Deiry
Jan 1, 1997·Molecular and Cellular Biology·M H Kubbutat, K H Vousden
Apr 8, 1998·Annual Review of Neuroscience·D W Choi, J Y Koh
Oct 28, 1998·Trends in Cell Biology·D H Lee, A L Goldberg
Dec 19, 1998·The EMBO Journal·A Ciechanover
Dec 29, 1998·The Journal of Cell Biology·J A JohnstonR R Kopito
Feb 26, 1999·The Journal of Biological Chemistry·P J KallioL Poellinger
May 4, 1999·The Journal of Cell Biology·W C WigleyP J Thomas
May 25, 1999·Cell·J D Laney, M Hochstrasser
Apr 14, 2000·European Journal of Pharmacology·C H KimY S Ahn
Jun 15, 2000·Journal of Neurochemistry·J N KellerW R Markesbery
Jun 17, 2000·Trends in Cell Biology·C Hirsch, H L Ploegh
Jul 6, 2000·Molecular Cell·R J SheaffB E Clurman
Aug 6, 2000·Free Radical Biology & Medicine·P K SomersU Saxena
Jan 4, 2001·Neuroscience Letters·K S McNaught, P Jenner
Jan 10, 2002·Biochemical and Biophysical Research Communications·Eric S HungnessPer-Olof Hasselgren
Feb 12, 2002·Nature Reviews. Molecular Cell Biology·Veronika Jesenberger, Stefan Jentsch
Mar 28, 2002·Physiological Reviews·Michael H Glickman, Aaron Ciechanover
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ashley I Bush, Rudolph E Tanzi
Aug 31, 2002·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·M AmiciA M Eleuteri
Nov 13, 2002·Biochemistry·Jean-Marc GabrielJean-Claude Jaton
Nov 21, 2002·The Journal of Biological Chemistry·Daniel StewartJawed Alam
Dec 14, 2002·Science·Chang-Wei LiuPhilip J Thomas
Jul 25, 2003·Toxicology and Applied Pharmacology·Chul Hoon KimYoung Soo Ahn

❮ Previous
Next ❯

Citations

Apr 12, 2014·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Sandra GötzeReinhard Saborowski
Dec 21, 2007·Molecular Biology of the Cell·Christine DidierNabila Jabrane-Ferrat
Nov 20, 2010·Journal of Translational Medicine·Erica JohnMichael T Lotze
Dec 22, 2010·Medical Microbiology and Immunology·Nadine WiesenerAndreas Henke
Aug 11, 2010·Omics : a Journal of Integrative Biology·Nathalie LandstetterKarl Kuchler
Dec 18, 2008·International Journal of Cancer. Journal International Du Cancer·Maria BerndtssonStig Linder
Oct 6, 2005·International Journal of Cancer. Journal International Du Cancer·Henrik LövborgRolf Larsson
Aug 25, 2015·Journal of Experimental & Clinical Cancer Research : CR·Alessia GarufiGabriella D'Orazi
Nov 14, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jens van WijngaardenClemens W G M Löwik
Jun 29, 2007·Molecular and Cellular Neurosciences·Eun Jung LeeKwang Chul Chung
Aug 22, 2006·Biochimica Et Biophysica Acta·Sanchayita Mitra, Edward Abraham
Aug 10, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Anne E O'DuffyBethAnn McLaughlin
Jan 28, 2015·Antimicrobial Agents and Chemotherapy·Dhiman Sankar PalRupak Datta
Oct 2, 2015·Journal of Korean Medical Science·Jiyoung KimJong-Wan Park
Jun 27, 2008·Neuroreport·Insook KimYoung Soo Ahn
Apr 25, 2019·International Journal of Molecular Sciences·Thais A SalesTeodorico C Ramalho
Jun 11, 2005·The Biochemical Journal·Petra KissAndor Udvardy
Jun 27, 2019·Proteomes·Bastien DalzonThierry Rabilloud
Dec 21, 2018·International Journal of Molecular Sciences·Karl KernsPeter Sutovsky
Jul 1, 2020·Chemical Society Reviews·A Paden King, Justin J Wilson
May 29, 2018·Nature Communications·Karl KernsPeter Sutovsky
Mar 22, 2007·The Journal of General Virology·K LankeF J M van Kuppeveld
Apr 11, 2020·Redox Biology·Juan Diego Hernández-CamachoIgnacio Navas-Enamorado
May 20, 2008·Archives of Biochemistry and Biophysics·Aktar Uzzaman ChouduriShinpei Yamada

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Cell Cycle Control & Proteolysis

Key regulators of cell cycle, including cyclins, cyclin dependent kinase inhibitors, DNA replication factors, are controlled by proteolysis. Discover the latest research on cell cycle control and proteolysis.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.