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

A CASE OF SPORADIC KARYOMEGALIC INTERSTITIAL NEPHRITIS WITH A NOVEL FAN1 GENE MUTATION: THE FIRST REPORT IN EAST ASIA. (ISN-WCN 2026) - "To assess the functional consequence of the novel FAN1 frameshift variant, wild-type and mutant FAN1 plasmids were transfected into HEK293 cells, and protein expression was evaluated by Western blot (WB) with or without the proteasome inhibitor MG132.Results Urinalysis showed no proteinuria or hematuria...Recognition of tubular karyomegaly in chronic interstitial nephritis without drug exposure or viral infection should prompt consideration of KIN. This case emphasizes the diagnostic value of integrating pathological and genetic, and biochemical assessments, enabling accurate diagnosis, prognostication, and genetic counseling."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Nephrology • Targeted Protein Degradation • CST3 • FAN1

Integrative single-cell, spatial, and bulk transcriptomics reveal an FMR1-FTO axis linked to the immune-excluded phenotype in gastric cancer. (PubMed, Front Immunol) - "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."

IO biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • CD8 • FMR1 • FTO

MUS81 inhibits cell proliferation and migration in breast cancer by promoting the expression of CDKN2A(p16INK4a). (PubMed, Am J Transl Res) - "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."

Journal • Breast Cancer • Oncology • Solid Tumor • CDKN2A • MUS81

Identification and Validation of RORC as a Circadian Rhythm-Related Biomarker in Gastric Cancer. (PubMed, Int J Gen Med) - "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."

Biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • ARID1A • RORC • TP53

MECHANISTIC INTERSECTION OF LRRK2 MUTATIONS AND PROTEOSTASIS IN PARKINSON'S DISEASE (ADPD 2026) - "This study aims to identify mechanisms regulating LRRK2 protein degradation, focusing on proteostasis factors involved in its turnover. 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

Myofibrillar protein accumulation but reduced protein synthesis in PDCD4-depleted myotubes. (PubMed, PLoS One) - "The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a nutrient/growth-factor sensitive positive regulator of skeletal muscle mass...In starved myotubes treated with the proteasome inhibitor MG132, accumulation of ubiquitinated proteins was attenuated in PDCD4-depleted cells...In summary, myofibrillar protein accumulation in PDCD4-depleted myotubes did not lead to improved intracellular Ca2+ handling, likely due to reduced energy level. Our data point to a pivotal role for PDCD4 in regulating myotube size."

Journal • Targeted Protein Degradation • PDCD4

Matrix density shapes early invasion and EWSR1::FLI1 protein dynamics in Ewing sarcoma (AACR 2026) - "In line with this, proteasome inhibition with MG132 prevents invasion onset without inducing major cell death, supporting proteasome-dependent regulation of early EwS invasion. Taken together, these findings identify an ECM-associated EWSR1::FLI1-low state as an early adaptive feature during invasion onset. Our model enables dissection of this regulation -from matrix sensing to active detachment- and suggests a role for proteasome-mediated mechanisms in shaping early metastatic traits in Ewing sarcoma."

Tumor mutational burden • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • EWSR1 • FLI1 • TMB

Discovery of pan-KRAS molecular glue degraders via protein-first coevolution-guided E3 ligase recruitment (AACR 2026) - "Target degradation was quantified by HiBiT luminescence, confirmed by automated capillary electrophoresis (Jess/WES) western blotting of both HiBiT-tagged and endogenous KRAS, and validated for proteasome dependence using MG132... Our coevolution-guided, protein-first MGD platform enables rapid discovery of small molecules that induce pan-KRAS degradation across major oncogenic mutants. These compounds achieve degradation of KRAS protein through a proteasome-dependent mechanism, distinguishing them from covalent KRASG12C inhibitors and RAS(ON) tri-complex inhibitors. The identified pan-KRAS molecular glue degraders represent a novel therapeutic modality with potential to address the majority of KRAS-driven cancers previously considered undruggable."

Oncology • KRAS

Investigating FOXC2-dependent mechanisms regulating stem cell Identity in breast cancer (AACR 2026) - "Pharmacologic PLK1 inhibition (Volasertib) reduces FOXC2 protein levels, and this loss is reversed by the proteasome inhibitor MG132, suggesting that PLK1-dependent phosphorylation stabilizes FOXC2. Live-cell imaging further indicates that FOXC2 is spatially regulated during mitosis and that phosphorylation may affect its chromatin association and inheritance. Collectively, our findings suggest PLK1-dependent phosphorylation of FOXC2 may stabilize the FOXC2 protein and influence its function during mitosis and regulate stem cell identity in daughter cells during cell division."

Breast Cancer • Embryonal Tumor • Oncology • Solid Tumor • Triple Negative Breast Cancer • FOXC2

Rational design of potent androgen receptor degraders via AI-assisted molecular modeling and validation of anti-tumor efficacy in prostate cancer (AACR 2026) - "The degradation was abolished by co-treatment with the proteasome inhibitor MG132, confirming a ubiquitin-proteasome-dependent mechanism...In summary, through AI-assisted molecular design and computational screening, we developed a potent AR degrader that efficiently induces proteasome-dependent AR degradation, suppresses AR transcriptional activity, and exhibits robust anti-tumor efficacy in vivo. These results highlight a promising therapeutic approach for advanced prostate cancer through targeted AR degradation."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CRBN • KLK3

A first-in-class potent EZH2 degrader, AXT-1003, exhibits robust anti-tumor activity across multiple lymphomas and solid tumors (AACR 2026) - "Several S-adenosylmethionine (SAM)-competitive EZH2 inhibitors, which suppress methyltransferase activity of EZH2, have clinically shown promising results in treating sarcoma and lymphoma, including the FDA-approved tazemetostat (EPZ-6438)...Meanwhile, AXT-1003 had no significant effect on EZH2 at transcriptional levels, and its protein expression was restored by MG-132 (proteasome inhibitor)...Notably, in the patient-derived organoid (PDO) models from ovarian clear cell carcinoma (OCCC) samples, AXT-1003 displayed superior efficacy compared with cisplatin or mevrometostat (PF-06821497), regardless of ARID1A status...Furthermore, the in vivo combination treatment of AXT-1003 with enzalutamide showed synergistic efficacy in a prostate cancer (LNCaP) CDX mice model. In conclusion, our preclinical data highlight the therapeutic potential of AXT-1003 and support its ongoing clinical evaluation in patients with EZH2-driven cancers."

Clear Cell Carcinoma • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Sarcoma • Solid Tumor • ARID1A • EZH2

Small-molecule stabilization of non-native c-Myc multimer drives degradation using an IDP-targeting discovery platform (AACR 2026) - "The proteasome inhibitor MG-132, the ubiquitin-activating enzyme inhibitor TAK-243, and the autophagy inhibitor Autophinib each rescued c-Myc levels after compound treatment, implicating both ubiquitin-proteasome and aggrephagy-like mechanisms. Structure-activity and pharmacophore analyses, together with structure-based design, yielded additional series with improved properties and activity (DC₅₀ < 1 µM). These data provide proof of concept that exploiting IDP conformational ensembles to stabilize degradable c-Myc assemblies can generate small-molecule c-Myc degraders and support further optimization of this platform toward safer, more selective anti-MYC therapeutics."

Breast Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • Triple Negative Breast Cancer • MYC • SDC1

Effects of ergosterol peroxide on proteostasis disruption in triple negative breast cancer cells (AACR 2026) - "Due to the lack of targeted therapies, TNBC patients typically undergo multimodality chemotherapy with cytotoxic agents like taxanes, anthracyclines, and cyclophosphamide...Moreover, EP significantly increases protein aggregation, although the signal detected for MG132 was greater...In summary, EP demonstrates the capacity to modulate proteostasis in TNBC cells. Further investigation is warranted to comprehensively characterize the intricate mechanistic pathways by which EP exerts its anticancer effects in this malignancy."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

SOX4 upregulation contributes to ovarian cancer initiation through a stress-adaptation program (AACR 2026) - "SOX4-induced cells showed synergistic reduction in cell proliferation and apoptosis when combined with MG132 or Tunicamycin...This process highlights a time-limited, stress-sensitive therapeutic window—before full adaptation, during which ER and proteasome challenges are especially effective. These findings position SOX4 as both a mechanistic driver of stress adaptation in HGSC carcinogenesis and a biomarker to select HGSC patients for targeted stress-modulating therapies."

Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • SOX4

SUMOylation regulates GATA2 stability to control uterine serous carcinoma invasion (AACR 2026) - "GATA2 half-life was measured using cycloheximide chase experiments paired with inhibitors of phosphorylation (staurosporine), acetylation (C646), SUMOylation (ML792), cysteine peptidase activity (N-Ethylmaleimide/NEM), and proteasome-dependent degradation (MG132)... USC GATA2 levels are determined by post-translational mechanisms. GATA2 protein has a rapid 60-minute half-life determined by SUMOylation and proteasome-mediated degradation. Depletion experiments support PIAS2 as the GATA2-targeting E3 SUMO ligase and SENP1 as the GATA2-targeting SUMO peptidase."

Endometrial Serous Adenocarcinoma • Oncology • Solid Tumor • Uterine Cancer • AURKA • GAPDH • GATA2 • PIAS4

CDK2 controls RIPK2 ubiquitination and stability in prostate cancer cells (AACR 2026) - "This study aims to address this knowledge gap by investigating the regulation of RIPK2 ubiquitination and degradation in PC cells, with a particular focus on CDK2, which we identified as a key mediator of RIPK2 regulation of the c-Myc oncoprotein. PC cells—22Rv1 (androgen receptor-positive) and PC3 (androgen receptor-negative)—were treated with two clinically evaluated, CDK2-selective inhibitors, INX-315 and PF-07104091...RIPK2 stability was assessed using cycloheximide (CHX) chase assays, and proteasomal degradation was evaluated with MG132 treatment...Cell cycle synchronization was achieved by serum starvation or treatment with Ro-3306, hydroxyurea, thymidine, or monastrol... Kinase-active CDK2 inhibits the K48-linked ubiquitination of RIPK2 and protects it from proteasomal degradation. This protection is potentially mediated by regulating the association between RIPK2 and its deubiquitinase YOD1 in PC cells. The findings support further investigation into the..."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CDK2 • MYC • RIPK2

Targeted degradation of DNA ligase IV through a double-stranded DNA-based PROTAC for precision radiosensitization (AACR 2026) - "NHEJ-P achieves near-complete loss of endogenous LIG4 at ~10 nM, verified by western blot and rescued by MG132, confirming proteasome dependence...Building on this foundation, we are conjugating NHEJ-P to trastuzumab using a site-directed enzymatic approach to generate t-NHEJ-P, a HER2-directed antibody-oligonucleotide conjugate (AOC) for tumor-restricted delivery. Planned studies will assess pharmacokinetics, tissue-selective LIG4 degradation, and radiosensitization in HER2⁺ xenografts, along with prospective safety in gastrointestinal, cardiac, pulmonary, and skin radiation-toxicity models. Together, these findings establish targeted LIG4 degradation as a new paradigm for DNA-damage-response modulation and lay the groundwork for next-generation, bystander-limited radiosensitizers that integrate molecular precision with translational safety."

Oncology • CRBN • RAD51 • TP53BP1

WEE1 reinforces C-MYC driven oncogenic programs through GSK3ß inhibition (AACR 2026) - "Cycloheximide chase assays revealed a shortened MYC half-life upon WEE1 inhibition, whereas the proteasome inhibitor MG132 rescued MYC degradation.Mechanistically, WEE1 inhibition activated GSK3β, a kinase required for MYC ubiquitination and proteasomal turnover...A high-throughput screen of 892 FDA-approved drugs identified Panobinostat as a synergistic partner of the WEE1 inhibitor MK1775... These findings define a WEE1-GSK3β-MYC signaling axis in which WEE1 stabilizes MYC and sustains MYC-driven oncogenic programs. WEE1 inhibition activates GSK3β, promoting proteasome-mediated MYC degradation. The combination of WEE1 inhibition and Panobinostat represents a promising therapeutic approach for MYC-driven EAC."

Esophageal Adenocarcinoma • Oncology • Solid Tumor • MYC • WEE1

A novel targeted protein degradation platform based on internalization-enhancing peptide for lysosomal degradation of cell-surface proteins (AACR 2026) - "To demonstrate its potential, Atezolizumab (ATZ), an FDA-approved monoclonal antibody targeting PD-L1, was used as a model...The decrease in PD-L1 was blocked by BafA1, a lysosomal proteolysis inhibitor, but not by MG132, a proteasome inhibitor—indicating that ATZ-IEP mediates lysosomal, rather than proteasomal, degradation. To assess the generality of this effect, Durvalumab (DUR), another FDA-approved anti-PD-L1 antibody, and HCC827 (NSCLC) cells were tested...In summary, ATZ-IEP mediates lysosomal degradation of PD-L1 and demonstrates broad applicability across antibodies and tumor types. Ongoing in vivo studies aim to confirm the efficacy of ATZ-IEP, further supporting the versatility of IEP as a novel TPD platform."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Development of polyHis-targeting chimeras (HisTACs) for targeted protein degradation (AACR 2026) - "MG-132 co-treatment fully blocked BRD4 depletion, confirming proteasome dependence...VHL-recruiting HisTACs also induced potent, isoform-selective BRD4 degradation with sub-micromolar efficacy toward the long isoform.To test the generalizability of this platform, we engineered a polyHis-HiBiT-tagged PSPC1 cell line—an RNA-binding protein lacking tractable ligands. Both CRBN- and VHL-based HisTAC degraders induced rapid, dose-dependent PSPC1 degradation, demonstrating the applicability of Ni²⁺-NTA-guided proximity to traditionally "undruggable" targets.Together, these results establish HisTAC degraders as a versatile, ligand-independent strategy for probing challenging cancer targets and accelerating degrader discovery and mechanistic studies in cancer research."

Oncology • BRD4 • CRBN

KPC1 regulates mesenchymal reprogramming in metastatic melanoma through ubiquitin-dependent degradation of ZEB1 (AACR 2026) - "Functional validation included siRNA knockdown, qRT-PCR, Western blotting, cycloheximide chase, MG132 treatment, ubiquitination assays, and wound-healing migration assays... KPC1 functions as a post-translational suppressor of MES-like reprogramming in metastatic melanoma by promoting ubiquitin-dependent degradation of ZEB1. Loss of KPC1 stabilizes ZEB1, activates MES transcriptional and phenotypic programs, and correlates with poor clinical outcomes. These findings identify KPC1 as a key regulator of melanoma cell-state plasticity and supports its potential utility as a theragnostic target."

Metastases • Melanoma • Oncology • Solid Tumor • CDH1 • CDH2 • RNF123 • ZEB1

Molecular Mechanisms Underlying the Alleviation of Aβ-Induced Toxicity by Edible Flower Buds of Hemerocallis citrina in Caenorhabditis elegans. (PubMed, Chem Biodivers) - "Notably, the proteasome inhibitor MG132 partially reversed HC-EA's anti-paralysis effect, suggesting that its action depends on proteasome activation and SKN-1-mediated oxidative stress mitigation. Collectively, HC-EA may attenuate Aβ toxicity by enhancing proteasome activity and antioxidant pathways, offering a potential protective effect against Alzheimer's disease (AD)."

Journal • Alzheimer's Disease • CNS Disorders

Hepatitis C Virus Core Induces p53 Ser-15 Phosphorylation to Facilitate E6-Associated Protein-Mediated Proteasomal Degradation of p53. (PubMed, Cells) - "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."

Journal • Hepatitis C • Infectious Disease • Inflammation • Oncology • Targeted Protein Degradation • CHEK2