ArticleBiochemical pharmacology2010
Proteasome inhibition up-regulates inflammatory gene transcription induced by an atypical pathway of NF-kappaB activation.
Article in Biochemical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Therapeutic inhibition of myeloperoxidase with AZD5904 attenuates disease progression in mouse models of early stage and relapsed multiple myeloma.Haematologica · 2026Article
- Baitong Decoction Ameliorates DSS-Induced Colitis via Modulation of STING and JAK/STAT Pathways.ACS omega · 2025Article
- Proteostasis in T cell aging.Seminars in immunology · 2023Review
- Intersection of the Ubiquitin-Proteasome System with Oxidative Stress in Cardiovascular Disease.International journal of molecular sciences · 2022Review
- Immunoproteasomes control activation of innate immune signaling and microglial function.Frontiers in immunology · 2022Article
- Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells.International journal of molecular sciences · 2021Article
- Increased co-expression of PSMA2 and GLP-1 receptor in cervical cancer models in type 2 diabetes attenuated by Exendin-4: A translational case-control study.EBioMedicine · 2021Article
- Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients.International journal of molecular sciences · 2020Article
- Article
- Molecular Insight Into the IRE1α-Mediated Type I Interferon Response Induced by Proteasome Impairment in Myeloid Cells of the Brain.Frontiers in immunology · 2019Article
- The effects of bortezomib on the ovariectomy applied rat uterus: A histopathological, stereological, and immunohistochemical study.Iranian journal of basic medical sciences · 2018Article
- Mechanisms of isolevuglandin-protein adduct formation in inflammation and hypertension.Prostaglandins & other lipid mediators · 2018Review
- Dendritic cells and isolevuglandins in immunity, inflammation, and hypertension.American journal of physiology. Heart and circulatory physiology · 2017Review
- Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury.Experimental lung research · 2015Article
- Redox-regulated pathway of tyrosine phosphorylation underlies NF-κB induction by an atypical pathway independent of the 26S proteasome.Biomolecules · 2015Article
- Therapeutic benefit of bortezomib on acute graft-versus-host disease is tissue specific and is associated with interleukin-6 levels.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2014Article
- Bortezomib therapy-related lung disease in Japanese patients with multiple myeloma: incidence, mortality and clinical characterization.Cancer science · 2014Article
- Proteasome inhibition by bortezomib increases IL-8 expression in androgen-independent prostate cancer cells: the role of IKKα.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Aging and immune function: molecular mechanisms to interventions.Antioxidants & redox signaling · 2011Review
- Inflammation as death or life signal in diabetic fracture healing.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2011Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Proteasome inhibition has become synonymous with inhibition of NF-kappaB activity. However, hyperactive NF-kappaB responses often accompany physiological conditions marked by proteasomal defects, i.e. advancing age, geriatric diseases, and bortezomib resistance. These paradoxical NF-kappaB responses are likely to be impervious to proteasomal defects because they stem from atypical NF-kappaB signaling induced by upstream mechanisms which are proteasome-independent. While this atypical pathway does not require proteasome for NF-kappaB nuclear translocation, a role for proteasome in regulating nuclear NF-kappaB remains unexplored. We now demonstrate that proteasome stringently controls transcription of inflammatory mediators regulated by this atypical NF-kappaB pathway. Proteolytic activity of the proteasome mediates the removal of the NF-kappaB subunit, p65/RelA, from inflammatory genes, thereby terminating atypical NF-kappaB-dependent transcriptional responses. For the first time, we demonstrate that both 19S and 20S components of the 26S proteasome complex are recruited to an inflammatory gene promoter; additionally, the 19S and 20S complexes appear to play distinct roles in the negative regulation of NF-kappaB-dependent transcription. By demonstrating that proteasome regulates the termination of atypical NF-kappaB-dependent transcriptional responses, these studies clearly indicate a novel, regulatory role for proteasome in atypical NF-kappaB signaling. Moreover, these results signal a potential interplay between lowered proteasomal function and increased inflammation and may explain why inflammation accompanies physiological conditions under which proteasomal function is compromised, such as during advancing age or following bortezomib treatment. Given this role for proteasome in inflammation resolution, restoration of proteasome function may constitute a novel mechanism for intervening in chronic inflammatory diseases.
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Registered trials
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.