Topic
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.
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TL;DR: It is shown that UBC9, a SUMO-conjugating enzyme, regulates ubiquitination and degradation of Nav1.5, and co-immunoprecipitation showed that U BC9 interacts with Nedd4-2, which acts as an E3 ubiquitin-protein ligase involved in ubiquitine-protein degradation and regulates Nav 1.5 expression levels in asumOylation-independent manner.
17 citations
TL;DR: This study ectopically expressed Abeta42 in the cytoplasm of SH-SY5Y neuroblastoma cells by expressing a fusion protein of GFP-tagged ubiquitin and Abeta 42 (GFPUb-Abeta42).
17 citations
TL;DR: The regulation of protein degradation is identified as an important factor in the recovery of cells from toxicity induced by classical DNA-damaging agents.
Abstract: Genome wide experiments indicate both proteasome- and vacuole-mediated protein degradation modulate sensitivity to classical DNA-damaging agents. Here, we show that global protein degradation is significantly increased upon methyl methanesulfonate (MMS) exposure. In addition, global protein degradation is similarly increased upon exposure to 4-nitroquinoline-N-oxide (4NQO) and UV and, to a lesser extent, tert-butyl hydroperoxide. The proteasomal inhibitor MG132 decreases both MMS-induced and 4NQO-induced protein degradation, while addition of the vacuolar inhibitor phenylmethanesulfonyl fluoride does not. The addition of both inhibitors grossly inhibits cell growth upon MMS exposure over and above the growth inhibition induced by MMS alone. The MMS-induced protein degradation response remains unchanged in several ubiquitin-proteasome and vacuolar mutants, presumably because these mutants are not totally deficient in either essential pathway. Furthermore, MMS-induced protein degradation is independent of Mec1, Mag1, Rad23, and Rad6, suggesting that the protein degradation response is not transduced through the classical Mec1 DNA damage response pathway or through repair intermediates generated by the base excision, nucleotide excision, or postreplication-DNA repair pathways. These results identify the regulation of protein degradation as an important factor in the recovery of cells from toxicity induced by classical DNA-damaging agents.
17 citations
TL;DR: Results suggest that the proteasome inhibitors activate CRE binding proteins consisting of c-Jun and ATF-2 through activating the JNK-c-Jun pathway, thereby inducing MIE protein synthesis in IMR-32 cells under the condition where NF-kappaB activity is inhibited.
17 citations
TL;DR: Hypoxia interferes with TGFβ signaling in macrophages by calpain-mediated proteolysis of the central signaling component SMAD2, substantiating the ability of calpain to degradeSMAD2.
Abstract: Under inflammatory conditions or during tumor progression macrophages acquire distinct phenotypes, with factors of the microenvironment such as hypoxia and transforming growth factor β (TGFβ) shaping their functional plasticity. TGFβ is among the factors causing alternative macrophage activation, which contributes to tissue regeneration and thus, resolution of inflammation but may also provoke tumor progression. However, the signal crosstalk between TGFβ and hypoxia is ill defined. Exposing human primary macrophages to TGFβ elicited a rapid SMAD2/SMAD3 phosphorylation. This early TGFβ-signaling remained unaffected by hypoxia. However, with prolonged exposure periods to TGFβ/hypoxia the expression of SMAD2 declined because of decreased protein stability. In parallel, hypoxia increased mRNA and protein amount of the calpain regulatory subunit, with the further notion that TGFβ/hypoxia elicited calpain activation. The dual specific proteasome/calpain inhibitor MG132 and the specific calpain inhibitor 1 rescued SMAD2 degradation, substantiating the ability of calpain to degrade SMAD2. Decreased SMAD2 expression reduced TGFβ transcriptional activity of its target genes thrombospondin 1, dystonin, and matrix metalloproteinase 2. Hypoxia interferes with TGFβ signaling in macrophages by calpain-mediated proteolysis of the central signaling component SMAD2.
17 citations