scispace - formally typeset
Search or ask a question
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.


Papers
More filters
Journal ArticleDOI
TL;DR: Blockade of NF-kappaB activation in microglia in vitro can decrease production of TNF-alpha and may prove to be a novel strategy for treating HIV-1 dementia.

34 citations

Journal ArticleDOI
09 Jan 2003-Oncogene
TL;DR: It is found that wtBRCA1 overexpressing DU-145 cell clones showed significantly decreased sensitivity to heat-induced cytotoxicity; and Brca1 mutant mouse embryo fibroblasts showed increasedensitivity to heat.
Abstract: The heat shock response is an evolutionarily conserved response to heat and other stresses that promotes the maintenance of key metabolic functions and cell survival. We report that exposure of human prostate (DU-145) and breast (MCF-7) cancer cells to heat (42°C) caused a rapid disappearance of the breast cancer susceptibility gene-1 (BRCA1) protein, starting at ≈1 h after the onset of heating and slightly lagging behind the increase in heat shock protein 70 (HSP70) levels. The heat-induced loss of BRCA1 occurred at the protein level, since: (1) BRCA1 mRNA expression was unaffected; and (2) the BRCA1 protein loss was also observed in DU-145 cells that expressed exogenous wild-type BRCA1 (wtBRCA1). In addition to heat regulation of BRCA1 protein levels, we also found that BRCA1 could modulate the heat shock response. Thus, wtBRCA1 overexpressing DU-145 cell clones showed significantly decreased sensitivity to heat-induced cytotoxicity; and Brca1 mutant mouse embryo fibroblasts showed increased sensitivity to heat. The DU-145 wtBRCA1 clones also showed increased expression of the small heat shock protein HSP27; and reporter assays revealed that wtBRCA1 stimulated a two to four-fold increase in HSP27 promoter activity, consistent with its ability to upregulate HSP27 mRNA and protein levels. In studies using epitope-tagged truncated BRCA1 proteins, the ability to stimulate the HSP27 promoter and to mediate heat-induced degradation required the amino-terminus but not the carboxyl-terminus of BRCA1. Although the heat-induced loss of BRCA1 appeared to be due to protein degradation, various protein metabolic agents (or combinations) failed to block this event, including: MG132 (a 26S proteasomal inhibitor), N-acetyl-leucyl-leucyl-norleucinal (a calpain inhibitor), z-VAD-fmk (a pan-caspase inhibitor), and ammonium chloride and chloroquine (which stabilize lysosomes). These findings suggest that in addition to its other functions, BRCA1 may participate in mammalian heat shock response pathways.

34 citations

Journal ArticleDOI
TL;DR: An oncogenic function of NQO1 in sustaining HCC cell proliferation through SIRT6/AKT/XIAP signaling pathway is revealed through inhibiting ubiquitin-mediated 26S proteasome degradation.
Abstract: Our previous study has demonstrated that NAD(P)H: quinone oxidoreductase 1 (NQO1) is significantly upregulated in human liver cancer where it potentiates the apoptosis evasion of liver cancer cell. However, the underlying mechanisms of the oncogenic function of NQO1 in HCC have not been fully elucidated. Expression of NQO1, SIRT6, AKT and X-linked inhibitor of apoptosis protein (XIAP) protein were measured by western blotting and immunohistochemistry. Additionally, the interaction between NQO1 and potential proteins were determined by immunoprecipitation assays. Furthermore, the effect of NQO1 and SIRT6 on tumor growth was determined in cell model and orthotopic tumor implantation model. We found that NQO1 overexpression in HCC enhanced SIRT6 protein stability via inhibiting ubiquitin-mediated 26S proteasome degradation. High level of SIRT6 reduced acetylation of AKT which resulted in increased phosphorylation and activity of AKT. Activated AKT subsequently phosphorylated anti-apoptotic protein XIAP at Ser87 which determined its protein stability. Reintroduction of SIRT6 or AKT efficiently rescued NQO1 knock-out-mediated inhibition of growth and induction of apoptosis. In orthotopic mouse model, NQO1 knock-out inhibited tumor growth and induced apoptosis while this effect was effectively rescued by SIRT6 overexpression or MG132 treatment partially. Collectively, these results reveal an oncogenic function of NQO1 in sustaining HCC cell proliferation through SIRT6/AKT/XIAP signaling pathway.

34 citations

Journal ArticleDOI
TL;DR: Investigating the molecular mechanisms by which AR inhibition prevents the hypoxia-induced human colon cancer cells growth and invasion indicates that AR mediates hypoxic signals, leading to tumor progression and invasion.

34 citations

Journal Article
Zhimei Gao1, Yayi Gao, Zhiyuan Li, Zuojia Chen, Daru Lu, Andy Tsun, Bin Li 
TL;DR: In this paper, the combination of transforming growth factor-beta (TGF-β) and IL-6 treatment (IL-6/TGFβ) can synergistically downregulate FOXP3 at the posttranslational level by promoting FoxP3 protein degradation.
Abstract: The forkhead family transcription factor FOXP3 is critical for the differentiation and function of CD4(+) CD25(+) regulatory T cells (Treg). How FOXP3 protein level is negatively regulated under the inflammatory microenvironment is largely unknown. Here we report that the combination of transforming growth factor-beta (TGF-β) and IL-6 treatment (IL-6/TGF-β) can synergistically downregulate FOXP3 at the posttranslational level by promoting FOXP3 protein degradation. In our FOXP3 overexpression model, we found that IL-6/TGF-β treatment upregulated IL-6R expression but did not affect the stability of FOXP3 mRNA. Moreover, we found that the proteasome inhibitor MG132 could inhibit IL-6/TGF-β-mediated downregulation of FOXP3 protein, which reveals a potential pathway for modulating Treg activity by preventing FOXP3 degradation during inflammation.

34 citations


Network Information
Related Topics (5)
Signal transduction
122.6K papers, 8.2M citations
90% related
Cell culture
133.3K papers, 5.3M citations
90% related
Gene expression
113.3K papers, 5.5M citations
88% related
Transcription factor
82.8K papers, 5.4M citations
88% related
Regulation of gene expression
85.4K papers, 5.8M citations
87% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202386
202270
202157
202059
201962
201848