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Pyrrolidine dithiocarbamate and zinc inhibit proteasome-dependent proteolysis

Authors
 Insook Kim  ;  Chul Hoon Kim  ;  Young Soo Ahn  ;  Chung Y Hsu  ;  Kwang Chul Chung  ;  Min Goo Lee  ;  Zheng Ai Chen  ;  Jun Jeong Choi  ;  Jinu Lee  ;  Joo Hee Kim 
Citation
 EXPERIMENTAL CELL RESEARCH, Vol.298(1) : 229-238, 2004 
Journal Title
 EXPERIMENTAL CELL RESEARCH 
ISSN
 0014-4827 
Issue Date
2004
MeSH
Centrosome/drug effects ; Centrosome/metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/metabolism ; Cysteine Endopeptidases/drug effects ; Cysteine Endopeptidases/metabolism* ; HeLa Cells ; Humans ; Ionophores/pharmacology ; Multienzyme Complexes/drug effects ; Multienzyme Complexes/metabolism* ; Nerve Tissue Proteins/drug effects ; Nerve Tissue Proteins/metabolism ; Peptide Hydrolases/drug effects ; Peptide Hydrolases/metabolism* ; Proteasome Endopeptidase Complex ; Proteins/metabolism* ; Pyrrolidines/pharmacology* ; Recombinant Fusion Proteins/drug effects ; Recombinant Fusion Proteins/metabolism ; Synucleins ; Thiocarbamates/pharmacology* ; Tumor Suppressor Protein p53/metabolism ; Ubiquitin/drug effects ; Ubiquitin/metabolism ; Zinc/metabolism ; Zinc/pharmacology* ; alpha-Synuclein
Keywords
Zinc ; Proteasomes ; p53 ; p21 ; α-Synuclein
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 UbG76V-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 α-synuclein. These results suggest that zinc may modulate cell functions through its action on the turnover of proteins that are susceptible to proteasome-dependent proteolysis.
Full Text
http://www.sciencedirect.com/science/article/pii/S0014482704002204
DOI
10.1016/j.yexcr.2004.04.017
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, In Sook(김인숙)
Kim, Joo Hee(김주희)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Ahn, Young Soo(안영수)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Chung, Kwang Chul(정광철)
Choi, Jun Jeong(최준정)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111571
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