MG132

Cycloheximide (CHX) chase and MG132 treatment showed that FMR1 depletion reduced FTO protein abundance and accelerated FTO turnover in an MG132-sensitive manner, consistent with a post-translational regulatory relationship. Collectively, our data support an FMR1-FTO module associated with the immune-excluded phenotype and nominate this axis as a potential vulnerability for disrupting stromal immune barriers. The FMR1-FTO axis may represent a candidate target for strategies aimed at relieving immune exclusion and improving immunotherapy sensitivity.

Furthermore, the modulation of p16INK4a expression by MUS81 was abolished by pretreatment with cycloheximide or MG132, suggesting that MUS81 stabilizes p16INK4a by preventing proteasome-mediated degradation. Collectively, these findings indicate that MUS81 works as a tumor suppressor in BC by inhibiting proliferation and migration through post-translational stabilization of p16INK4a.

Drug sensitivity analysis indicates that the RORC gene is responsive to agents such as VX-680, MG-132, and Sunitinib. Cell biology experiments have confirmed that RORC overexpression significantly diminishes the proliferation, invasion, and migration capabilities of gastric cancer cells. Integrating bioinformatics and cell biology experiments suggests that RORC, a gene associated with rhythm regulation, acts as a tumor suppressor gene that is underexpressed in gastric cancer, thereby serving as a potential biomarker and therapeutic target for this malignancy.

Proteasomal inhibition with MG132 confirmed that HCV Core and E6AP act together to regulate p53 levels via the proteasome. Importantly, HCV Core-induced p53 phosphorylation was essential for E6AP-mediated degradation, as shown by the impairment of degradation in the presence of the ATM inhibitor KU-55933. E6AP also targeted p53 phosphorylated at Ser-15 by etoposide, as well as phosphomimetic mutants such as p53 S15D, but not non-phosphorylatable mutants such as p53 S15A. These findings suggest that HCV Core-induced p53 phosphorylation enhances E6AP-mediated degradation while preventing MDM2 from targeting p53, thereby maintaining p53 levels that support cell survival, viral replication, and potentially oncogenesis in human hepatocytes.

Based on our findings, we define a key role for SENP3 in colorectal cancer progression and suggest it as a viable target for therapeutic intervention.

In our study, the PR-619 inhibitor caused a decrease in the HIF2α protein level in 786-O, OS-RC-2, and SW839 cells, and MG132 treatment increased HIF2α protein expression after PR-619 treatment...We also confirmed that USP10 expression was upregulated in kidney cancer and had a positive correlation with HIF2α expression in RCC patient samples. Our results suggest that USP10 promotes HIF2α stability.

RS-1 induced dose- and time-dependent GPX4 degradation in HT1080 fibrosarcoma cells (DC50 = 8.9 nM), mechanistically dependent on the ubiquitin-proteasome system, as confirmed by MG-132 cotreatment...In vivo, RS-1 demonstrated potent antitumor efficacy in a 4T1 murine mammary carcinoma model, achieving 80.5% tumor growth inhibition (TGI). These findings establish RS-1 as a novel GPX4-targeted degrader with translational potential, offering a promising strategy to exploit ferroptosis in cancer therapy.

In addition, treatment enhanced odontoblast differentiation and mineralization, as evidenced by the upregulated expression of Nestin, collagen type I alpha-1, transforming growth factor beta 1, runt-related transcription factor 2, osteopontin, and osteocalcin. Moreover, at 42 days, MG132-treated samples exhibited distinct dentin bridge formation.

Treatment with DT-061 combined with its inactive competitive antagonist, DT-766, and the proteasome inhibitor, MG-132, reversed this effect on the loss of N-Myc protein expression, suggesting that PP2A-B56α modulation affects N-Myc stability via the proteasomal degradation pathway. In a xenograft model, we observed tumor growth inhibition upon DT-061 treatment, along with a reduction in N-Myc protein expression in vivo. Combined, these results highlight the importance of the PP2A tumor suppressor in regulating MYCN oncogenic signaling and open new potential treatment regimens for high-risk neuroblastoma patients.

SRT-1720 induces oxidative stress and apoptosis in leukemic lymphocytes through SIRT1-independent pathway(s). In contrast, it enhances antioxidant defense in normal lymphocytes through a SIRT1-dependent pathway. These findings highlight the potential of SRT-1720 as an adjuvant to chemotherapy in T-ALL, particularly in drug combinations demonstrating strong synergism, which may allow dose reduction and decreased toxicity.

Rescue experiments used N-acetylcysteine (NAC) and chloroquine (CQ)...CQ but not MG-132 increased CD276 expression in ESCC cells...SLC1A5 enhances CD276 stability by suppressing ROS-autophagy signaling, promoting ESCC progression. Targeting glutamine metabolism to enhance CD276 degradation might be a novel therapeutic strategy for ESCC.

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.