Pyrrolidine dithiocarbamate and zinc inhibit proteasome-dependent proteolysis

Insook Kim, Chul Hoon Kim, Joo Hee Kim, Jinu Lee, Jun Jeong Choi, Zheng Ai Chen, Min Goo Lee, Kwang Chul Chung, Chung Y. Hsu, Young Soo Ahn

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)229-238
Number of pages10
JournalExperimental Cell Research
Volume298
Issue number1
DOIs
Publication statusPublished - 2004 Aug 1

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this