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MG132

About: MG132 is a research topic. Over the lifetime, 1499 publications have been published within this topic receiving 56589 citations. The topic is also known as: MG132 & Z-Leu-leu-leu-al.


Papers
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Journal ArticleDOI
TL;DR: The observations reveal an important role of the UPS in multiple steps of the coronavirus infection cycle and identify the UPS as a potential drug target to modulate the impact of CoV infection.
Abstract: The ubiquitin-proteasome system (UPS) is a key player in regulating the intracellular sorting and degradation of proteins In this study we investigated the role of the UPS in different steps of the coronavirus (CoV) infection cycle Inhibition of the proteasome by different chemical compounds (ie, MG132, epoxomicin, and Velcade) appeared to not only impair entry but also RNA synthesis and subsequent protein expression of different CoVs (ie, mouse hepatitis virus [MHV], feline infectious peritonitis virus, and severe acute respiratory syndrome CoV) MHV assembly and release were, however, not appreciably affected by these compounds The inhibitory effect on CoV protein expression did not appear to result from a general inhibition of translation due to induction of a cellular stress response by the inhibitors Stress-induced phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) generally results in impaired initiation of protein synthesis, but the sensitivity of MHV infection to proteasome inhibitors was unchanged in cells lacking a phosphorylatable eIF2alpha MHV infection was affected not only by inhibition of the proteasome but also by interfering with protein ubiquitination Viral protein expression was reduced in cells expressing a temperature-sensitive ubiquitin-activating enzyme E1 at the restrictive temperature, as well as in cells in which ubiquitin was depleted by using small interfering RNAs Under these conditions, the susceptibility of the cells to virus infection was, however, not affected, excluding an important role of ubiquitination in virus entry Our observations reveal an important role of the UPS in multiple steps of the CoV infection cycle and identify the UPS as a potential drug target to modulate the impact of CoV infection

110 citations

Journal ArticleDOI
TL;DR: The results suggest that following preconditioning ischemia, Bim is rapidly degraded by the ubiquitin-proteasome system, resulting in rapid ischemic tolerance, which suggests that the rapid degradation of cell death-promoting proteins by the proteasome pathway may represent a novel therapeutic strategy to reduce cell damage following neuropathological insults, e.g. stroke.

110 citations

Journal ArticleDOI
TL;DR: Sub substrate-induced loss of D2 activity is due to proteasomal degradation of the enzyme and requires interaction with the catalytic center of the protein.
Abstract: Type 2 iodothyronine deiodinase (D2) catalyzes the first step in thyroid hormone action, the deiodination of T4 to T3 . Endogenous D2 activity is posttranslationally regulated by substrate that accelerates its degradation through the ubiquitin-proteasome pathway. To understand how D2 activity correlates with D2 protein during its normal decay and rT3-induced down-regulation, HEK-293 cells, transiently expressing human D2, were labeled with Na75SeO3 and then treated with 100μ m cycloheximide (CX), 30 nm rT3, and/or 10 μm MG132, a specific proteasome inhibitor, for 2–4 h. D2 protein and enzyme activity changed in parallel, disappearing with a half-life of 2 h in the presence of CX, or 1 h when CX + rT3 were combined. Treatment with MG132 blocked these effects. We created selenocysteine (Sec) 133 to cysteine (Cys) or alanine (Ala) D2 mutants, without changing Sec 266. The CysD2 activity and protein levels were also parallel, with a similar half-life of approximately 2 h, whereas the rT3-induced D2 down-regul...

110 citations

Journal ArticleDOI
TL;DR: Data show that Ser-129-phosphorylated a-Syn is targeted to the proteasome pathway in a ubiquitin-independent manner, in addition to undergoing deph phosphorylation.

109 citations

Journal ArticleDOI
TL;DR: Evidence is provided that 5-HT, internalized through the 5- HT transporter, is transamidated to RhoA by transglutaminase, which in turn is responsible for Akt activation and contraction inhibition in arterial smooth muscle.

109 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202386
202270
202157
202059
201962
201848