MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute - LARVOL DELTA

Regulation of ER-Resident Transcription Factor NFE2L1 in HEK293 Cells. (PubMed, Biol Pharm Bull) - "NFE2L1 protein expression in wild-type HEK293 cells was negligible, but MG132/bortezomib treatment induced Endo H-resistant two bands...Treatment with the valosin containing protein (VCP) inhibitor CB-5083 increased NFE2L1 expression, but deficiencies in other ERAD-associated factors (ER degradation-enhancing α-mannosidase-like protein 2 (EDEM2), thioredoxin domain-containing protein 11 (TXNDC11), gp78, ring finger protein 5 (RNF5), ring finger protein 185 (RNF185), and USP19) did not affect its expression...Therefore, we constructed NFE2L1 genes with mutations in the site where NFE2L1 is cleaved by DDI2 and in the four asparagine residues where N-glycosylation occurs, and found that the high molecular weight form, especially a hypoglycosylated mutant, tended to be more unstable. Taken together, this study using several ERAD disordered models shows that the regulation of NFE2L1 is different in some ways from the regulation of CREB3/ATF6 family, and these findings..."

Journal • ATF6 • TXNDC11 • USP19

Targeted Sensitization of Leukemic T-cells to Anticancer Drugs by SIRT1 Agonist SRT-1720. (PubMed, Anticancer Res) - "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."

Journal • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • SIRT1

NEDD4L knockdown enhances synovial fibroblast migration, invasion, and inflammatory factor secretion via Wnt/β-Catenin signaling activation. (PubMed, Clin Rheumatol) - "NEDD4L modulates the migration, invasion, and pro-inflammatory cytokine secretion of RA-FLSs via the Wnt/β-catenin signaling pathway, suggesting its potential as a therapeutic target for RA. Key Points • NEDD4L knockdown activates Wnt/β-catenin pathway (DVL2, GSK3β, β-catenin). • Promotes IL-6/TNF-α secretion and cell invasiveness. • NEDD4L overexpression shows opposite effects. • Potential therapeutic target for RA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • IL6 • TNFA

Research Progress of Proteasome Inhibitor MG132 in Treatment of Gynecologic Malignant Tumors. (PubMed, J Biochem Mol Toxicol) - "Among proteasome inhibitors, MG132 has garnered extensive attention in gynecologic oncology due to its multifaceted mechanisms, including cell cycle regulation, NF-κB signaling inhibition, and modulation of p53 activity. This review consolidates recent research on the therapeutic potential of MG132 in gynecologic malignant tumors, with a focus on its molecular mechanisms of action."

Journal • Review • Gynecologic Cancers • Oncology • Solid Tumor • Targeted Protein Degradation

Nemo-like kinase modulates glucocorticoid-induced erythroid progenitor differentiation by regulating stability of the glucocorticoid receptor. (PubMed, FEBS J) - "NLK overexpression downregulated levels of GR in a kinase-dependent manner across HEK293T, K562, and MEL cells, an effect reversed by MG132 or a ubiquitination-defective mutant. Conversely, dexamethasone upregulated NLK, suppressing GR and suggesting a feedback loop. Thus, NLK-mediated GR downregulation constrains erythropoiesis, and its inhibition by OTS167 promotes erythroid expansion, revealing a targetable pathway in erythroid disorders."

Journal • Genetic Disorders • Hematological Disorders • Targeted Protein Degradation • CD34 • TFRC

Supercharging-enhanced nDIA-MS enables global profiling of drug-induced proteome solubility shifts. (PubMed, Nat Commun) - "The drugs elicit distinct and sometimes opposing solubility shifts; for instance, MG132 insolubilizes HSF1, ML-792 solubilizes SP100 and insolubilizes PLOR3G, and SMAD2 shows opposite responses to those two treatments. These results reveal widespread, drug-induced remodeling of the protein solubility landscape and establish solubility profiling by nDIA-MS as a broadly applicable platform for uncovering protein state transitions and cellular responses to perturbation."

Journal • Addiction (Opioid and Alcohol) • HSF1 • SMAD2

Glutamine transporter SLC1A5 inhibits autophagy-mediated CD276 degradation to promote esophageal cancer progression. (PubMed, Cancer Biol Ther) - "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."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • CD276 • SLC1A5

Dss1 facilitates Rad51 recruitment downstream of BRCA2/Brh2 in response to DNA damage. (PubMed, DNA Repair (Amst)) - "However, DSS1 foci rarely colocalize with BRCA2 foci. Finally, Dss1 focus formation is inhibited by treatment with the proteasome inhibitor MG132, in both U. maydis and DT40 cells, suggesting a role of ubiquitin in homology-dependent repair."

Journal • Targeted Protein Degradation • BRCA2 • RAD51 • RAD52

Soybean Phosphomethylpyrimidine Synthase GmTHIC Contributes to Thiamine Biosynthesis and Salt Tolerance. (PubMed, J Agric Food Chem) - "Interestingly, the degradation is not attenuated by the protease inhibitor MG132, indicating that GmPUB21 ubiquitinates GmTHIC possibly via a 26S proteasome-independent degradation system. In addition, exogenous application of thiamine effectively alleviates salt stress symptoms in soybean plants, reduces reactive oxygen species accumulation, and thereby enhances salt tolerance. These results reveal that GmTHIC is required for thiamine biosynthesis and salt tolerance in soybean."

Journal • Targeted Protein Degradation

Hypoxic mesenchymal stem cell-Derived Exosomal circPTP4A2 improves granulosa cell mitochondrial function via YBX1. (PubMed, Cell Mol Life Sci) - "These results establish the circPTP4A2/YBX1 axis as a critical mediator of the therapeutic efficacy of H-Exs for POI, providing both mechanistic insights and a translational framework for exosome-based regenerative strategies."

Journal • Women's Health • HIF1A • YBX1

Differential roles of proteasome and autophagy in α-synuclein and E46K oligomer clearance: insight into the modulatory effects of the dopamine metabolite DOPAC. (PubMed, Int J Biol Macromol) - "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."

Journal • CNS Disorders • Metabolic Disorders • Movement Disorders • Neuroblastoma • Oncology • Parkinson's Disease • Solid Tumor • Targeted Protein Degradation • LAMP1

Afatinib inhibits esophageal squamous cell carcinoma by regulating ferroptosis and NRF2 protein homeostasis. (PubMed, Int Immunopharmacol) - "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."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • Targeted Protein Degradation • GPX4

Hypoxia-Inducible Factor-1α, a Novel Molecular Target for a 2-Aminopyrrole Derivative: Biological and Molecular Modeling Study. (PubMed, Cancers (Basel)) - "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."

Journal • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CASP3 • FLT1 • HIF1A

MECHANISTIC INTERSECTION OF LRRK2 MUTATIONS AND PROTEOSTASIS IN PARKINSON'S DISEASE (ADPD 2026) - " A CRISPRi screen targeting ~3,500 proteostasis genes identified pathways regulating LRRK2 turnover in doxycycline-inducible GFP-LRRK2 HEK-293T cells...To investigate how NPLOC4 regulates LRRK2, cells were treated with MG132 (proteasomal inhibitor) and CuET (NPLOC4 inhibitor), followed by biochemical fractionation... Together, these studies suggest VCP-NPLOC4-UFD1L complex and RAD23A, independently or cooperatively, contribute to LRRK2 degradation via proteasomal pathways. Ongoing studies aim to determine how modulation of these ubiquitin processing factors rescues neurodegenerative phenotypes."

CNS Disorders • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation • LRRK2

DEVELOPMENT OF RABBIT MONOCLONAL ANTIBODIES AND PAIR-BASED ASSAYS TO INTERROGATE TDP43 DYSFUNCTION (ADPD 2026) - "Cells were untreated, treated with a proteasome inhibitor (MG-132), or treated with sodium arsenite to induce oxidative stress, TDP43 phosphorylation, and TDP43 aggregation... CST continues to expand its portfolio of offerings to investigate TDP43 dysfunction, developing antibodies to key TDP43 PTMs, and disease-relevant targets affected downstream. These reagents will enable researchers to examine the consequences of TDP43 dysfunction in immortalized cells, iPSCs, and patient-derived tissues and biofluids utilizing methods that include techniques like western blot, immuno-based imaging, and pair-based assays."

Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation • STMN2 • TARDBP

INHIBITION OF THE PROTEASOME PATHWAY SUPPRESSES TAU AGGREGATION AND HYPERPHOSPHORYLATION INDUCED BY PATHOLOGICAL TAU (ADPD 2026) - "In contrast, inhibition of autophagy with bafilomycin A1 enhanced AD P-tau–induced aggregation and phosphorylation, but did not prevent the suppression of seeding by proteasome inhibition with MG132... AD P-tau drives hyperphosphorylated tau aggregation and disrupts both UPS and AP pathways. Proteasome inhibition suppresses AD P-tau-seeded aggregation and phosphorylation through regulation of PP2Ac methylation, independently of the AP pathway."

Alzheimer's Disease • CNS Disorders • Targeted Protein Degradation • PPP2CA

Mechanism of periplogenin in promoting Nrf2 degradation and inducing ferroptosis to inhibit bladder cancer (PubMed, Zhongguo Zhong Yao Za Zhi) - "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."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • GPX4 • HMOX1 • SLC7A11

Mechanism of ginsenoside Rb_1 in ameliorating hypoxia/reoxygenation injury in H9c2 cardiomyocytes through CTR1 ubiquitination-mediated regulation of cuproptosis (PubMed, Zhongguo Zhong Yao Za Zhi) - "To explore the degradation pathway of CTR1, this study treated the cells with cycloheximide and the proteasome inhibitor MG132...This protective effect may be associated with the inhibition of apoptosis and the regulation of protein ubiquitination-mediated degradation pathways. This study elucidates a novel mechanism by which G-Rb1 ameliorates cardiomyocyte injury through the CTR1 ubiquitination-mediated regulation of the cuproptosis pathway, providing a theoretical foundation for the development of cardioprotective drugs."

Journal • Reperfusion Injury • Targeted Protein Degradation • FDX1 • LIAS • RB1

PSMD12 Overexpression Promotes Lung Adenocarcinoma Progression via Ubiquitin-Proteasome Pathway Dysregulation. (PubMed, Cancer Sci) - "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."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CDK1 • PSMD12

Regulation of autophagy-Ferroptosis crosstalk by the SLC7A11-GPX4 axis during sperm capacitation. (PubMed, Theriogenology) - "Pharmacology combined with immunoblotting and GPX4 activity assays demonstrated that proteasome inhibition (MG132) preserves GPX4 abundance and activity, whereas USP8 inhibition (DUB-IN-2) increases GPX4 ubiquitination and reduces its level and activity; conversely, the GPX4 inhibitor RSL3 nearly abolishes activity. Autophagy blockade with chloroquine, assessed by LC3/p62 immunoblotting and SLC7A11 immunofluorescence, disrupted polarized SLC7A11 localization and, as shown by cystine-uptake and glutamate-efflux assays, impaired transporter function. Ferroptotic stress markers-ROS (BDP 581/591), labile Fe2+ (RhoNox-1), and malondialdehyde (TBARS assay)-were increased by erastin or RSL3, and In vitro fertilization assays further showed that pharmacological disruption of the autophagy-SLC7A11-GPX4 axis reduced sperm-oocyte binding and early embryo cleavage. Together, these data indicate that ubiquitin-linkage remodeling and deubiquitination cooperate with autophagy-dependent..."

Journal • Gynecology • Targeted Protein Degradation • GPX4 • SLC7A11 • USP8

Determining the Half-Life of MHC Class I Molecules by Blocking Protein Synthesis Using Cycloheximide. (PubMed, Methods Mol Biol) - "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."

Journal • Oncology • CD8

dentification and characterization of novel PAX4 variants in patients with suspected MODY9. (PubMed, BMJ Open Diabetes Res Care) - "This study expands the spectrum of PAX4 variants and provides novel mechanistic insights into the pathogenesis of MODY9. Our results highlight the importance of assessing protein-level consequences for variant interpretation and support the integration of functional assays into MODY genetic diagnostic workflows."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Novel Homozygous Mutation in PMFBP1 Associated with Acephalic Spermatozoa Defects. (PubMed, Biomedicines) - "Protein expression and stability were analyzed by Western blot and cycloheximide (CHX)/MG132 assays...This study expands the clinical mutational spectrum of PMFBP1-associated male infertility and provides valuable insights for the genetic diagnosis of ASS patients. Additionally, these findings may lay a foundation for the choice of therapeutic strategies targeting PMFBP1-related ASS."

Journal • Gynecology • Infertility • Sexual Disorders

ADSCs-EVs Carrying circITCH Inhibit Pyroptosis of Renal Tubular Epithelial Cells and Alleviate LPS-Induced Acute Kidney Injury. (PubMed, FASEB J) - "After treatment with cycloheximide or MG132, HuR protein expression or ubiquitination level was detected by western blot...Mechanistically, low expression of circITCH weakens the interaction between HuR and β-TrCP, reduces HuR ubiquitination, and enhances the interaction between HuR and RBM15 mRNA, thereby increasing m6A modification on CRBN and promoting CRBN expression in an IGF2BP1-dependent manner. Collectively, ADSCs-EVs alleviate renal tubular epithelial cell pyroptosis by carrying circITCH, ultimately reducing LPS-induced AKI."

Journal • Acute Kidney Injury • Nephrology • Renal Disease • Targeted Protein Degradation • CRBN • IGF2BP1 • RBM15

A Cuproptosis-Related lncRNA Signature Predicts Prognosis and Shapes the Immune Landscape in Primary Lower-Grade Glioma. (PubMed, Genet Res (Camb)) - "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."

Biomarker • IO biomarker • Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • TP63