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DRUG:

MG132

i
Other names: MG132, MG-132
Company:
Dorothy M. Davis Heart and Lung Research Institute, Jilin University
Drug class:
Proteasome inhibitor
9d
FAK inhibition suppresses breast cancer progression via DNA methylation-mediated DAB2 gene reactivation. (PubMed, bioRxiv)
We further showed that FAK-I reduced DNMT3A expression in breast cancer cells and that treatment with the proteasome inhibitor MG132 prevented loss of DNTM3A protein stability...Immunostaining of 4T1 tumors showed FAK-I decreased DNMT3A, DNA methylation (5-methylcytosine, 5-mC), and increased DAB2 expression. Taken together, these data suggest that nuclear FAK-mediated regulation of DNMT3A can alter the epigenetic landscape and induce tumor suppressor gene expression.
Journal • Epigenetic controller
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DNMT3A (DNA methyltransferase 1) • DAB2 (DAB Adaptor Protein 2)
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MG132
13d
The antioxidative effect of STAT3 involved in cellular vulnerability to isoflurane. (PubMed, BMC Neurosci)
These findings indicate that specific regulation of STAT3 was closely related with the cellular vulnerability to isoflurane via an antioxidative pathway.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3)
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MG132
18d
Inhibition of colorectal cancer aggressiveness by Oleanolic acid through Nur77 degradation. (PubMed, Phytomedicine)
We revealed a new regulatory effect of OA in CRC tumorigenesis via PPARγ-mediated Nur77 ubiquitin degradation.
Journal
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PPARG (Peroxisome Proliferator Activated Receptor Gamma)
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MG132
22d
RSK1 dependency in FLT3-ITD acute myeloid leukemia. (PubMed, Blood Cancer J)
Using cycloheximide, MG-132, and ubiquitination assays, we further demonstrate mechanistically that RSK1 regulates FLT3-ITD activity, and protein stability through deubiqutinase USP1, which we identify as a second dependency. Lastly, RSK1 inhibition utilizing a first-in-class RSK inhibitor, PMD-026, that is currently undergoing Phase 2 development for breast cancer, diminished leukemic disease burden in MV4-11 xenograft and syngeneic Flt3ITDTet2KO leukemia models. These findings illustrate an unconventional and promising therapeutic strategy targeting FLT3-ITD leukemia.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • RPS6 (Ribosomal Protein S6) • USP1 (Ubiquitin Specific Peptidase 1)
|
MG132 • PMD-026
23d
MG132 inhibits proliferation and induces apoptosis of acute lymphoblastic leukemia via Akt/FOXO3a/Bim pathway. (PubMed, Hum Exp Toxicol)
These findings suggest that MG132 exerts potent anti-leukemic effects through modulation of the Akt/FOXO3a/Bim axis, offering a promising therapeutic avenue for treating ALL.
Journal
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BCL2L11 (BCL2 Like 11) • FOXO3 (Forkhead box O3)
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MG132
24d
USP5-dependent HDAC1 promotes cisplatin resistance and the malignant progression of non-small cell lung cancer by regulating RILP acetylation levels. (PubMed, Thorac Cancer)
USP5-dependentstabilization of HDAC1 contributed to cisplatin resistance and the malignancy of NSCLC by diminishing the levels of RILP acetylation, which suggested that targeting the HDAC1-USP5axis might represent a novel therapeutic strategy for overcoming DDP resistance in NSCLC patients.
Journal
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ABCC1 (ATP Binding Cassette Subfamily C Member 1) • HDAC1 (Histone Deacetylase 1) • USP5 (Ubiquitin Specific Peptidase 5)
|
cisplatin • MG132
1m
Discovery of potent hypoxia-inducible factor-1α (HIF-1α) degraders by proteolysis targeting chimera (PROTAC). (PubMed, Bioorg Chem)
Additionally, this degradation was inhibited by the proteasome inhibitor MG132. As a part of the ongoing effort to develop HIF-1 inhibitors, targeting the degradation of HIF-1α may offer an effective treatment strategy against solid tumors.
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit)
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HIF1A overexpression • HIF1A expression
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MG132
1m
Rac1 GTPase Regulates the βTrCP-Mediated Proteolysis of YAP Independently of the LATS1/2 Kinases. (PubMed, Cancers (Basel))
In PC cells, the inhibition of Rac1 leads to a time-dependent decline in YAP protein, which could be blocked by proteosome inhibitor MG132... These results reveal Rac1 as an oncogenic KRAS effector that contributes to YAP stabilization in PC cells. They also show that this regulation of YAP by Rac1 requires the SCFβTrCP ligase but occurs independently of the LATS1/2 kinases.
Journal
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KRAS (KRAS proto-oncogene GTPase) • RAC1 (Rac Family Small GTPase 1) • LATS1 (Large Tumor Suppressor Kinase 1)
|
KRAS mutation
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MG132
1m
SOX17 expression in ovarian clear cell carcinoma. (PubMed, J Ovarian Res)
Polyubiquitinated bands of SOX17 were observed in MG132 treated OVTOKO, but not in OVISE or RMG-V OCCC cells...These findings indicate that SOX17 is not uniformly and heterogeneously expressed in OCCCs, independent of ARID1A deficiency. Impaired ubiquitin-mediated proteasome degradation may stabilize SOX17 in some OCCC cells.
Journal
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ARID1A (AT-rich interaction domain 1A) • SOX17 (SRY-Box Transcription Factor 17)
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ARID1A mutation
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MG132
1m
DDX5-Targeting Fragile X Mental Retardation Protein Regulates the Wnt/β-catenin Signaling Pathway to Promote Epithelial Mesenchymal Transition in Breast Cancer (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban)
The regulatory effect of FMRP on DDX5 protein expression was assessed using the protein synthesis inhibitor cycloheximide (CHX) and proteasome inhibitor MG132...On the other hand, the expression of these proteins was reversed by combined FMRP overexpression (P<0.05). FMRP targets DDX5 and promotes BC cell migration and EMT via the activation of the Wnt/β-catenin signaling pathway.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDH1 (Cadherin 1) • VIM (Vimentin) • CDH2 (Cadherin 2) • DDX5 (DEAD-Box Helicase 5) • SNAI2 (Snail Family Transcriptional Repressor 2) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
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MYC expression • CDH1 expression • VIM expression • ZEB1 expression
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MG132
2ms
The carcinogenesis of esophageal squamous cell cancer is positively regulated by USP13 through WISP1 deubiquitination. (PubMed, Biofactors)
ESCC cell lines (KYSE150 and TE10) were treated with the proteasome inhibitor MG-132, followed by siRNA screening of deubiquitinases (DUBs) to identify regulators of WISP1...Furthermore, knockdown of USP13 or WISP1 impaired the activation of the Wnt/CTNNB1 signaling pathway and reduced immune checkpoint marker expression, indicating a mechanism by which USP13 promotes immune evasion in ESCC. USP13 stabilizes WISP1 through deubiquitination, enhancing ESCC progression by activating the Wnt/CTNNB1 pathway and promoting immune evasion, making USP13 a potential therapeutic target in ESCC.
Journal
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CTNNB1 (Catenin (cadherin-associated protein), beta 1) • USP13 (Ubiquitin Specific Peptidase 13)
|
MG132
2ms
Yes-associated protein indispensably mediates hirsutine-induced inhibition on cell growth and Wnt/β-catenin signaling in colorectal cancer. (PubMed, Phytomedicine)
HT exhibits anticancer activity against CRC probably by inhibiting Wnt/β-catenin signaling, with YAP playing an indispensible role during the process, highlighting HT as a potential novel candidate drug for CRC therapy.
Journal • PARP Biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1) • AXIN1 (Axin 1)
|
MG132
2ms
NF-кB promotes aggresome formation via upregulating HDAC6 and in turn maintaining Vimentin cage. (PubMed, Am J Physiol Cell Physiol)
Remarkably, chemical inactivation of NF-кB synergized MG132-induced cell mortality. All the findings suggest that NF-кB dictates aggresome assembly via upregulating HDAC6, and NF-кB inhibitor may serve as a potential drug potentiating proteasome inhibitor medicine-induced cytotoxicity during the treatment of cancer cells.
Journal
|
VIM (Vimentin) • HDAC6 (Histone Deacetylase 6)
|
MG132
3ms
Regulatory mechanism of TRIM21 in sepsis-induced acute lung injury by promoting IRF1 ubiquitination. (PubMed, Clin Exp Pharmacol Physiol)
The mice were infected with lentivirus and treated with proteasome inhibitor MG132...Overexpression of IRF1 or silencing TREM2 reversed the improvement of TRIM21 overexpression on lung injury in mice. In conclusion, TRIM21 reduced IRF1 expression by ubiquitination to improve TREM2 expression and ameliorate sepsis-induced ALI.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • IRF1 (Interferon Regulatory Factor 1) • TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) • TRIM21 (Tripartite Motif Containing 21)
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IRF1 expression
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MG132
3ms
MG132-mediated Suppression of the Ubiquitin-proteasome Pathway Enhances the Sensitivity of Endometrial Cancer Cells to Cisplatin. (PubMed, Anticancer Agents Med Chem)
MG132 enhances the therapeutic efficacy of cisplatin in human EC cells by suppressing the ubiquitin- proteasome pathway, reducing cell viability, enhancing apoptosis, and shifting the inflammatory response. These findings highlighted the potential of MG132 as an adjuvant in endometrial cancer chemotherapy. Further research is needed to explore detailed mechanisms and clinical applications of this combination therapy.
Journal
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IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CASP3 (Caspase 3) • IL13 (Interleukin 13) • IL1B (Interleukin 1, beta)
|
cisplatin • MG132
3ms
A novel hydrophobic tag leads to the efficient degradation of programmed death-ligand 1. (PubMed, RSC Med Chem)
Meanwhile, the reduction of PD-L1 protein levels by Z2d/Z3d was counteracted by MG132, which indicated that Z2d/Z3d degraded PD-L1 through the proteasome pathway. Moreover, the molecular modeling results indicated that the HyT group of Z2d or Z3d extended the surface of the protein to mimic the misfold. Importantly, our work also identified a novel HyT, which could be applied to develop the HyTTD for other target proteins.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression
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MG132
3ms
Kindlin-2 regulates the oncogenic activities of integrins and TGF-β in triple-negative breast cancer progression and metastasis. (PubMed, Oncogene)
Treatment of Kindlin-2-deficient cells with the proteasome inhibitor MG-132 restored the expression of both β1-Integrin and TβRI...This study identifies a novel function of Kindlin-2 in stabilizing the β1-Integrin:TβRI complexes and regulating their downstream oncogenic signaling. The translational implications of these findings are substantial, potentially unveiling new therapeutically targeted pathways crucial for the treatment of TNBC tumors.
Journal
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TGFB1 (Transforming Growth Factor Beta 1)
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MG132
3ms
EP4 receptor agonist CAY10598 upregulates ROS-dependent Hsp90 cleavage in colorectal cancer cells. (PubMed, Free Radic Res)
Our results show that CAY10598 decreases the levels of client proteins of Hsp90 in HCT116 cells, an effect reversible by pretreatment with the ROS scavenger N-acetyl cysteine (NAC) or the proteasome inhibitor MG132, indicating that the degradation is likely driven by ROS...Additionally, CAY10598 suppressed the growth of HCT116 cells implanted in mice. Our findings reveal that CAY10598 induces apoptosis in cancer cells by a novel mechanism involving the ROS-dependent cleavage of Hsp90, thereby inhibiting the function of crucial Hsp90 client proteins.
Journal
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EGFR (Epidermal growth factor receptor) • JAK2 (Janus kinase 2) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
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MG132
3ms
Sodium butyrate blocks the growth of colorectal cancer by inhibiting the aerobic glycolysis mediated by SIRT4/HIF-1α. (PubMed, Chem Biol Interact)
By employing cycloheximide (CHX), MG132, and chloroquine (CQ), we investigated whether NaB affects HIF-1α protein levels via the autophagy pathway. Furthermore, a human colorectal cancer xenograft model confirmed that butyric acid inhibited tumor growth in vivo, correlating with SIRT4 and HIF-1α modulation. In conclusion, our findings indicate that NaB hinders colorectal cancer progression by disrupting aerobic glycolysis mediated by SIRT4/HIF-1α.
Journal
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LDHA (Lactate dehydrogenase A) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • SIRT4 (Sirtuin 4) • SLC2A1 (Solute Carrier Family 2 Member 1)
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HIF1A expression
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MG132 • chloroquine phosphate
4ms
Design, synthesis, and evaluation of antitumor activity in Pseudolaric acid B Azole derivatives: Novel and potent angiogenesis inhibitor via regulation of the PI3K/AKT and MAPK mediated HIF-1/VEGF signaling pathway. (PubMed, Eur J Med Chem)
This inhibitory effect on HIF-1α was corroborated by experiments utilizing the protease inhibitor MG-132 and protein synthesis inhibitor CHX, indicating that compound M2 diminishes HIF-1α levels by reducing its synthesis...In vivo studies demonstrated that compound M2 exhibited low toxicity and effectively curbed tumor growth. Immunohistochemistry analyses validated that compound M2 effectively suppressed the expression of HIF-1α and VEGF in tumor tissues, underscoring its potential as a promising therapeutic agent for targeting tumor angiogenesis.
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
HIF1A expression • VEGFA expression
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MG132
4ms
Tetrapeptide repeat domain 36 (TTC36) inhibits the inflammatory response of HK2 cells by enhancing the expression of IκBα to inhibit the activation of NF-κB signaling pathway (PubMed, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi)
IκBα protein expression level was further analyzed by Western blot after being treated with cycloheximide (CHX) and MG132...Conclusion Overexpression of TTC36 inhibits the inflammatory response of HK2 cells, reduces cell apoptosis, promotes proliferation, and strengthens tight junctions. The mechanism may be to inhibit the activation of NF-κB signaling pathway by enhancing the expression of IκBα, thereby reducing the cell damage caused by inflammatory response.
Journal • IO biomarker
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • CCL2 (Chemokine (C-C motif) ligand 2) • PCNA (Proliferating cell nuclear antigen) • IL1B (Interleukin 1, beta) • NFKBIA (NFKB Inhibitor Alpha 2) • TJP1 (Tight Junction Protein 1)
|
MG132
4ms
Glucose inhibits the inflammatory response in goose fatty liver by increasing the ubiquitination level of PKA. (PubMed, J Anim Sci)
Moreover, goose primary hepatocytes were co-treated with glucose, harringtonine and carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132)...In summary, glucose may inhibit the inflammatory response in goose fatty liver by increasing the ubiquitination level of PKA. Additionally, RNF135 and KCMF1 may be involved in the regulation of PKA ubiquitination level as E3 ubiquitination ligases.
Journal
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TNFA (Tumor Necrosis Factor-Alpha)
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MG132
4ms
Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties. (PubMed, Sci Rep)
Here, we used an integrated drug repositioning approach based on transcriptomics data and structure-based virtual screening to identify compounds with gene signatures similar to three known proteasome inhibitors (PIs; bortezomib, MG-132, and MLN-2238)...Using this approach, we identified six compounds with PI properties ((-)-kinetin-riboside, manumycin-A, puromycin dihydrochloride, resistomycin, tegaserod maleate, and thapsigargin)...As shown with bortezomib, only manumycin-A, puromycin dihydrochloride, and tegaserod maleate resulted in excessive accumulation of ubiquitinated proteins and elevated HMOX1 expression. Taken together, our integrated drug repositioning approach and subsequent in vitro validation studies identified six compounds demonstrating properties similar to proteasome inhibitors.
Journal
|
HMOX1 (Heme Oxygenase 1)
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bortezomib • Ninlaro (ixazomib) • MG132
4ms
The 'ABC' of split-nanoluciferase HIF heterodimerization bioassays: Applications, benefits & considerations. (PubMed, Biochem Pharmacol)
This study shows that the application of similar or diverse assay protocols allows to detect various influences on HIF heterodimerization as a key signaling event in the oxygen sensing pathway: increased HIF heterodimerization (roxadustat, MG-132), decreased HIF heterodimerization (PX-478, ibuprofen) and direct (HIF isoform-selective) heterodimerization inhibiting effects (PT-2385). Specific and general considerations include cell-based, technical and disease/drug-related aspects (e.g., non-specific effects, color interference). In summary, the versatility of these bioassays offers benefits in widespread applications regarding drug discovery and pharmacological characterization of various therapeutics, applying either the same or optimized experimental protocols.
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit)
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MK-3795 • MG132 • Evrenzo (roxadustat) • PX-478
5ms
Silencing of tropomodulin 1 inhibits acute myeloid leukemia cell proliferation and tumor growth by elevating karyopherin alpha 2-mediated autophagy. (PubMed, Pharmacol Res)
Silencing TMOD1 also inhibited tumor growth by elevating KPNA2-mediated autophagy in nude mice bearing MOLM-13 xenografts. Collectively, our data demonstrated that TMOD1 could be a novel therapeutic target for AML treatment.
Journal
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KPNA2 (Karyopherin Subunit Alpha 2)
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dorsomorphin (Compound C) • MG132
5ms
Inhibition of the ubiquitin-proteasome system reduces the abundance of pyruvate dehydrogenase kinase 1 in cultured myotubes. (PubMed, J Muscle Res Cell Motil)
In L6 myotubes treated with PYR-41, chloroquine increased the abundance of the epidermal growth factor receptor, but did not prevent the suppression of PDK1. Collectively, our results suggest that cultured myotubes degrade PDK1 via a pathway that cannot be inhibited by MG132, PYR-41, and/or chloroquine.
Journal
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EGFR (Epidermal growth factor receptor) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • PDK1 (Pyruvate Dehydrogenase Kinase 1)
|
MG132 • chloroquine phosphate
5ms
Prognostic significance of exportin-5 in hepatocellular carcinoma. (PubMed, World J Gastrointest Oncol)
Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.
Journal
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CD4 (CD4 Molecule)
|
paclitaxel • MG132
5ms
Negative Regulation of CPSF6 Suppresses the Warburg Effect and Angiogenesis Leading to Tumor Progression Via c-Myc Signaling Network: Potential Therapeutic Target for Liver Cancer Therapy. (PubMed, Int J Biol Sci)
Furthermore, c-Myc degradation by CPSF6 depletion was disturbed by FBW7 depletion or treatment with the proteasomal inhibitor MG132. Consistently, immunohistochemistry showed that CPSF6 depletion reduced the growth of Hep3B cells in BALB/c mice in orthotopic and xenograft tumor models by inhibiting tumor microenvironment-associated proteins. Overall, these findings suggest that CPSF6 enhances the Warburg effect for immune escape and angiogenesis, leading to cancer progression via c-Myc, mediated by the HK, PD-L1, and VEGF networks, with synergistic potential with sorafenib as a molecular target for liver cancer therapy.
Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CD4 (CD4 Molecule) • GZMB (Granzyme B) • CPSF6 (Cleavage And Polyadenylation Specific Factor 6) • PKM (Pyruvate Kinase M1/2)
|
sorafenib • MG132
5ms
STAT5B Suppresses Ferroptosis by Promoting DCAF13 Transcription to Regulate p53/xCT Pathway to Promote Mantle Cell Lymphoma Progression. (PubMed, Biologics)
The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132...Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH. STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.
Journal
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STAT5B (Signal Transducer And Activator Of Transcription 5B) • GPX4 (Glutathione Peroxidase 4)
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MG132
6ms
Cyclopeptide RA-V from Rubia yunnanensis restores activity of Adagrasib against colorectal cancer by reducing the expression of Nrf2. (PubMed, Pharmacol Res)
The results of molecular mechanisms showed that RA-V suppressed Nrf2 protein through the ubiquitin-proteasome-dependent degradation, leading to the induction of oxidative and ER stress, and DNA damage in CRC cell lines. Consequently, RA-V reverses the resistance to MRTX849 by inhibiting the Nrf2/GLS1 axis, which shows the potential for further developing into one of novel adjuvant therapies of MRTX849.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
|
Krazati (adagrasib) • MG132
6ms
REST Promotes Autophagy in Gastric Cancer by Transcriptionally Activating FABP6 to Inhibit the Akt/mTOR Signaling Pathway. (PubMed, Front Biosci (Landmark Ed))
REST positively regulates autophagy and negatively affects the Akt/mTOR signaling pathway in GC cells in a FABP6-dependent manner, providing valuable insights into regulatory networks involving FABP6 and REST.
Journal
|
FABP6 (Fatty Acid Binding Protein 6)
|
LY294002 • MG132
6ms
TRIM8 Promotes Proliferation, Invasion, and Migration of Cervical Cancer Cells by Ubiquitinating and Degrading SOCS1. (PubMed, Biochem Genet)
Protein immunoprecipitation assay was employed to examine TRIM8's binding with SOCS1, and the ubiquitination level of SOCS1 was determined after MG132 treatment...Inhibition of SOCS1 partially reversed the inhibitory effects of si-TRIM8 on the proliferation, invasion, and migration of CC cells. In conclusion, TRIM8 enhances CC cell proliferation, invasion, and migration via ubiquitination-mediated degradation of SOCS1.
Journal
|
SOCS1 (Suppressor Of Cytokine Signaling 1) • PCNA (Proliferating cell nuclear antigen)
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MG132
6ms
C-MYC-activated lncRNA SNHG20 accelerates the proliferation of diffuse large B cell lymphoma via USP14-mediated deubiquitination of β-catenin. (PubMed, Biol Direct)
Taken together, our results suggested that c-MYC-activated SNHG20 accelerated the proliferation and increased the apoptosis resistance of DLBCL cells via USP14-mediated deubiquitination of β-catenin. The c-MYC/SNHG20 positive feedback loop may be a new target for anti-DLBCL treatment.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • USP1 (Ubiquitin Specific Peptidase 1) • USP14 (Ubiquitin Specific Peptidase 14)
|
MG132
7ms
LncRNA HOXC-AS3 accelerates malignant proliferation of cervical cancer cells via stabilizing KDM5B. (PubMed, J Cancer Res Clin Oncol)
Nucleus-located lncRNA HOXC-AS3 facilitated malignant proliferation of CC cells via stabilization of KDM5B protein levels.
Journal
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ARID1B (AT-Rich Interaction Domain 1B) • KDM5B (Lysine Demethylase 5B) • TRIM37 (Tripartite Motif Containing 37)
|
MG132
7ms
Pepsinogen C Interacts with IQGAP1 to Inhibit the Metastasis of Gastric Cancer Cells by Suppressing Rho-GTPase Pathway. (PubMed, Cancers (Basel))
PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion.
Journal
|
IQGAP1 (IQ Motif Containing GTPase Activating Protein 1)
|
MG132
7ms
The Synergistic Effect of Reduced Graphene Oxide and Proteasome Inhibitor in the Induction of Apoptosis through Oxidative Stress in Breast Cancer Cell Lines. (PubMed, Int J Mol Sci)
Reduced graphene oxide (rGO) and a proteasome inhibitor (MG-132) are some of the most commonly used compounds in various biomedical applications...At the same time, both mitochondrial and receptor apoptosis pathways are activated. These studies provided new information on the molecular mechanisms of apoptosis in the ZR-75-1 and MDA-MB-231 breast cancer cell lines.
Preclinical • Journal
|
CASP8 (Caspase 8) • CASP9 (Caspase 9)
|
MG132
8ms
Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation. (PubMed, J Cancer)
The function of HACE1 in RAC1 protein ubiquitination was validated using the proteasome inhibitor MG132...Intriguingly, TRIP12 inhibition blocked HACE1-driven RAC1 ubiquitination and mitigated the inhibitory effects of HACE1 on ESCA cells, alleviating tumor growth in the tumor-bearing nude mouse model. HACE1 expression was downregulated in ESCA cells, suggesting that it curbs ESCA progression by inducing RAC1 protein degradation through TRIP12-mediated ubiquitination.
Journal
|
RAC1 (Rac Family Small GTPase 1) • TRIP12 (Thyroid Hormone Receptor Interactor 12) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
|
MG132
8ms
Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells. (PubMed, J Pharmacol Sci)
Antioxidants N-acetylcysteine and EUK-8 attenuated MG132-induced apoptosis. It was also found that MG132 treatment increased the expression of NOX5, a NOX family member, and that siRNA-mediated silencing of NOX5 and BAPTA-AM, which inhibits NOX5 by chelating calcium, suppressed MG132-induced apoptosis and production of reactive oxygen species in SH-SY5Y cells. These results suggest that MG132 induces apoptosis in SH-SY5Y cells through the production of superoxide anion by NOX5.
Journal
|
NOX5 (NADPH Oxidase 5)
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MG132
8ms
Regulation of Mertk Surface Expression via ADAM17 and γ-Secretase Proteolytic Processing. (PubMed, Int J Mol Sci)
Using chimeric Flag-Mertk-EGFP-Myc reporter receptors, we confirm that inhibitors of γ-secretase and MG132, which inhibits the 26S proteasome, stabilize the intracellular fragment of Mertk without evidence of nuclear translocation. Finally, the treatment of cells with active γ-carboxylated Gas6, but not inactive Warfarin-treated non-γ-carboxylated Gas6, regulates a distinct proteolytic itinerary-involved receptor clearance and lysosomal proteolysis. Together, these results indicate that pleotropic and complex proteolytic activities regulate Mertk ectodomain cleavage as a homeostatic negative regulatory event to safeguard against the overactivation of Mertk.
Journal
|
MERTK (MER Proto-Oncogene, Tyrosine Kinase) • GAS6 (Growth arrest specific 6) • ADAM17 (ADAM Metallopeptidase Domain 17) • GLI2 (GLI Family Zinc Finger 2)
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MERTK expression
|
MG132
8ms
Apoptotic Effect of Isoimpertorin via Inhibition of c-Myc and SIRT1 Signaling Axis. (PubMed, Int J Mol Sci)
Furthermore, Isoimperatorin suppressed the overexpression of c-Myc by the proteasome inhibitor MG132 and also disturbed cycloheximide-treated c-Myc stability in Huh7 cells. Overall, these findings support the novel evidence that the pivotal role of c-Myc and SIRT1 is critically involved in Isoimperatorin-induced apoptosis in HCCs as potent molecular targets in liver cancer therapy.
Journal • PARP Biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CASP3 (Caspase 3) • CDK2 (Cyclin-dependent kinase 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • SIRT1 (Sirtuin 1)
|
MYC overexpression • MYC expression • CCND1 expression • CCNE1 expression • CDK2 expression • CDK6 expression
|
MG132
8ms
Dicoumarol attenuates NLRP3 inflammasome activation to inhibit inflammation and fibrosis in knee osteoarthritis. (PubMed, Mol Med Rep)
Mechanistic studies demonstrated that dicoumarol did not affect NF‑κB signaling, but it did directly interact with NOD‑like receptor protein 3 (NLRP3) to promote its protein degradation, which could be reversed by MG132, but not NH4Cl...Furthermore, the inflammation and fibrosis of the knee joints were inhibited in rats. In conclusion, the present findings demonstrated that dicoumarol could impede the progression of KOA by inhibiting NLRP3 activation, providing a potential treatment strategy for KOA.
Journal
|
IL18 (Interleukin 18) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3)
|
MG132
8ms
TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis. (PubMed, Int J Biol Sci)
Cycloheximide chase assay and MG132 treatment were conducted to analyze protein stability... TIE1 expression in cervical cells exerts a tumor-promoting effect, which is at least in part dependent on its interaction with Basigin. These findings have revealed a TIE2-independent mechanism of TIE1, which may provide a new biomarker for cervical cancer progression, and a potential therapeutic target for the treatment of cervical cancer patients.
Journal
|
EGF (Epidermal growth factor) • BSG (Basigin (Ok Blood Group))
|
MG132