ArticleThe Journal of biological chemistry2014
Regulation of PSMB5 protein and β subunits of mammalian proteasome by constitutively activated signal transducer and activator of transcription 3 (STAT3): potential role in bortezomib-mediated anticancer therapy.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 77 citations in OpenAlex.
- Tofacitinib blocks IFN-regulated biomarker genes in skin fibroblasts and keratinocytes in a systemic sclerosis trial.JCI insight · 2022Trial
- Disentangling cell-intrinsic and cell-extrinsic factors underlying evolution.Cell genomics · 2025Article
- Augment proteasome inhibitor efficacy activates CD8Cell reports. Medicine · 2025Article
- N -Acetyl-Tryptophan in Acute Kidney Injury after Cardiac Surgery.Journal of the American Society of Nephrology : JASN · 2025Article
- The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells.Current issues in molecular biology · 2025Article
- Remodeling the Tumor Immune Environment in Breast Cancer via Bortezomib-based Combination Therapy.International journal of biological sciences · 2025Article
- Autophagy and oxidative stress modulation mediate Bortezomib resistance in prostate cancer.PloS one · 2024Article
- Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation.Acta biochimica et biophysica Sinica · 2023Article
- Role of NFE2L1 in the Regulation of Proteostasis: Implications for Aging and Neurodegenerative Diseases.Biology · 2023Review
- Spin column-based peptide fractionation alternatives for streamlined tandem mass tag (SL-TMT) sample processing.Journal of proteomics · 2023Article
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- REGγ promotes mantle cell lymphoma cell apoptosis by downregulating NF-κB signaling.Translational cancer research · 2023Article
- PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma.FEBS open bio · 2022Article
- Upregulated Proteasome Subunits in COVID-19 Patients: A Link with Hypoxemia, Lymphopenia and Inflammation.Biomolecules · 2022Article
- A Redox-Silent Analogue of Tocotrienol May Break the Homeostasis of Proteasomes in Human Malignant Mesothelioma Cells by Inhibiting STAT3 and NRF1.International journal of molecular sciences · 2022Article
- Review
- Article
- Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation.Biomolecules · 2021Review
- Expanding the role of proteasome homeostasis in Parkinson's disease: beyond protein breakdown.Cell death & disease · 2021Review
- Trash Talk: Mammalian Proteasome Regulation at the Transcriptional Level.Trends in genetics : TIG · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-proteasome system facilitates the degradation of ubiquitin-tagged proteins and performs a regulatory role in cells. Elevated proteasome activity and subunit expression are found in several cancers. However, the inherent molecular mechanisms responsible for increased proteasome function in cancers remain unclear despite the well investigated and defined role of the mammalian proteasome. This study was initiated to elucidate the mechanisms involved in the regulation of β subunits of the mammalian proteasome. Suppression of STAT3 tyrosine phosphorylation coordinately decreased the mRNA and protein levels of the β subunits of the 20 S core complex in DU145 cells. Notably, PSMB5, a molecular target of bortezomib, was shown to be a target of STAT3. Knockdown of STAT3 decreased PSMB5 protein. Inhibition of phospho-STAT3 substantially reduced PSMB5 protein levels in cells expressing constitutively active-STAT3. Accumulation of activated STAT3 resulted in the induction of PSMB5 promoter and protein levels. In addition, a direct correlation was observed between the endogenous levels of PSMB5 and constitutively active STAT3. PSMB5 and STAT3 protein levels remained unaltered following the inhibition of proteasome activity. The EGF-induced concerted increase of β subunits was blocked by inhibition of the EGF receptor or STAT3 but not by the PI3K/AKT or MEK/ERK pathways. Decreased proteasome activities were due to reduced protein levels of catalytic subunits of the proteasome in STAT3-inhibited cells. Combined treatments with bortezomib and inhibitor of STAT3 abrogated proteasome activity and enhanced cellular apoptosis. Overall, we demonstrate that aberrant activation of STAT3 regulates the expression of β subunits, in particular PSMB5, and the catalytic activity of the proteasome.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.