MG132

Mechanistic studies revealed that E46K/DOPAC aggregates were preferentially degraded via the ubiquitin-proteasome system (UPS), as proteasome inhibition with MG132 enhanced toxicity and intracellular accumulation. In contrast, autophagy inhibition by chloroquine paradoxically reduced toxicity, indicating redirection toward UPS-mediated degradation...Overall, our results demonstrate that DOPAC reshapes the biophysical and toxicological properties of Syn aggregates, especially E46K species, by promoting less harmful oligomers and enhancing proteostatic clearance. These findings highlight DOPAC as a promising modulator of Syn aggregation and pathology.

This study is the first to demonstrate that afatinib inhibits ESCC cell growth in vivo and in vitro by inducing ferroptosis, and that the regulatory axis Nrf2/xCT/GPX4 is involved in this process. The results of this study provide a novel mechanism for afatinib mediated anti-ESCC activity.

The downregulation of HIF-1α expression in 2-ANPC-treated cancer cells was due to enhanced proteasome-mediated degradation, whereas the proteasome inhibitor MG-132 effectively reversed this downregulation...Lastly, using various computational tools, we identified four potential binding sites for 2-ANPC to interact with HIF-1α, HIF-1β, and the p300 complex. Collectively, we show here, for the first time, that HIF-1α is a novel molecular target for the 2-aminopyrrole derivative (2-ANPC), thereby illustrating it as a potential scaffold for the development of potent chemotherapeutic agents with anti-angiogenic activity.

The regulatory mechanism of PPG on Nrf2 was further investigated using cycloheximide(CHX) to inhibit de novo protein synthesis, the proteasome inhibitor MG132 to block proteasomal degradation, and co-immunoprecipitation to assess Nrf2 ubiquitination...In vivo, PPG significantly suppressed tumor growth and reduced the expression of Ki67, GPX4, and Nrf2 in xenograft tumors compared with the control group. PPG induces ferroptosis in bladder cancer cells by promoting Nrf2 ubiquitination and proteasomal degradation, thereby inhibiting tumor cell growth.

Cycloheximide chase and MG132 assays confirmed that PSMD12 stabilized CDK1 by inhibiting proteasome-mediated degradation...PSMD12 promoted LUAD progression by modulating CDK1 ubiquitination and enhancing cell cycle progression. These findings suggest that PSMD12 is a promising molecular target for future LUAD therapies.

Additionally, we incorporated MG132, a proteasomal degradation inhibitor, to examine the impact of the proteasome on MHC I degradation. Furthermore, we detail a method for calculating the half-life of MHC I molecules by fitting the degradation data into a one-phase decay model.

Several prospective drugs targeting samples with high scores were predicted, namely, MG-132, PLX-4720, AZD6482, and BMS-536924. Moreover, experiments conducted in vitro demonstrated that knockdown of the expression of the CRLs TPRG1-AS1 and LYRM4-AS1 might impair the migration and proliferation capacity of glioma cells. Taken together, these results indicate that CRLs are linked to prognosis and immune characteristics in LGG and give innovative therapeutic methods for individuals with LGG across different risk stratifications.

AAMP overexpression is associated with malignant clinical features of HCC and promotes epithelial-mesenchymal transition and metastasis of HCC cells partly by stabilizing RhoA expression.

MG132 eliminated the inhibition of propofol on HDAC1-mediated DGCR8 deacetylation...As a conclusion, propofol inhibited the stem characteristics and growth of NSCLC tumor by regulating the translocation and expression of HDAC1. This study provides potential targets and treatment options for the treatment of advanced NSCLC tumors.

Our findings reveal a novel mechanism whereby CUL2 promotes PC progression and ferroptosis resistance through regulation of the KEAP1-NRF2 axis. CUL2 overexpression enhances cellular antioxidant capacity and maintains mitochondrial integrity, thereby conferring broad resistance to ferroptosis-inducing conditions. This study suggests that targeting the CUL2-NRF2 axis to enhance ferroptosis sensitivity might represent a promising therapeutic strategy for PC treatment.

The proteasome inhibitor MG132 confirmed that fisetin accelerates β-catenin and MITF degradation. Additionally, inhibition of the PI3K/AKT pathway by LY294002 or the ERK pathway by PD98059 reversed fisetin's reduction of tyrosinase activity and melanin synthesis, further verifying the participation of these pathways. Computational docking integrated with deep learning-based CNN scoring revealed that fisetin interacts with PKCα, β-catenin, tyrosinase, and TYRP1. Collectively, these findings suggest that fisetin exerts multi-targeted inhibitory effects on melanogenesis, highlighting its potential as a therapeutic and cosmetic agent for hyperpigmentation.

Additionally, MG132 inhibited the differentiation of endothelial progenitor cells (EPCs) into smooth muscle cells (SMCs) and reduced the levels of inflammatory cytokines, including high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). Moreover, MG132 effectively suppressed the expression of NF-κB P65 and its downstream signaling pathway, intercellular adhesion molecule-1 (ICAM-1).