ArticleThe Journal of biological chemistry2013
Overexpression of USP14 protease reduces I-κB protein levels and increases cytokine release in lung epithelial cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 71 citations in OpenAlex.
- Novel Therapeutic Targets of Endothelial Inflammation in Acute Lung Injury and Acute Respiratory Distress Syndrome.Journal of respiratory biology and translational medicine · 2026Article
- Identification of AKOS, a Chikungunya virus inhibitor, as a USP14 inhibitor for colorectal cancer treatment.Acta pharmacologica Sinica · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Review
- The deubiquitinase USP40 preserves endothelial integrity by targeting the heat shock protein HSP90β.Experimental & molecular medicine · 2024Article
- Roles of ubiquitin-specific proteases in inflammatory diseases.Frontiers in immunology · 2024Review
- USP14 inhibition promotes recovery by protecting BBB integrity and attenuating neuroinflammation in MCAO mice.CNS neuroscience & therapeutics · 2023Article
- Targeting ubiquitin specific proteases (USPs) in cancer immunotherapy: from basic research to preclinical application.Journal of experimental & clinical cancer research : CR · 2023Review
- Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC).Cell death and differentiation · 2023Article
- USP14 promotes colorectal cancer progression by targeting JNK for stabilization.Cell death & disease · 2023Article
- Mitophagy in atherosclerosis: from mechanism to therapy.Frontiers in immunology · 2023Review
- USP14 regulates cell cycle progression through deubiquitinating CDK1 in breast cancer.Acta biochimica et biophysica Sinica · 2022Article
- USP14 promotes pyroptosis of human annulus fibrosus cells derived from patients with intervertebral disc degeneration through deubiquitination of NLRP3.Acta biochimica et biophysica Sinica · 2022Article
- Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer.Nature communications · 2022Article
- Article
- USP14 Regulates Cancer Cell Growth in a Fatty Acid Synthase-Independent Manner.International journal of molecular sciences · 2021Article
- Article
- Lipopolysaccharide reduces USP13 stability through c-Jun N-terminal kinase activation in Kupffer cells.Journal of cellular physiology · 2021Article
- Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The ubiquitin-proteasome system is the major pathway of non-lysosomal intracellular protein degradation, playing an important role in a variety of cellular responses including cell division, proliferation, and apoptosis. Ubiquitin-specific protease 14 (USP14) is a component of proteasome regulatory subunit 19 S that regulates deubiquitinated proteins entering inside the proteasome core 20 S. The role of USP14 in protein degradation is still controversial. Several studies suggest that USP14 plays an inhibitory role in protein degradation. Here, in contrast, overexpression of USP14 induced I-κB degradation, which increased cytokine release in lung epithelial cells. Overexpression of HA-tagged USP14 (HA-USP14) reduced I-κB protein levels by increasing the I-κB degradation rate in mouse lung epithelial cells (MLE12). I-κB polyubiquitination was reduced in HA-USP14-overexpressed MLE12 cells, suggesting that USP14 regulates I-κB degradation by removing its ubiquitin chain, thus promoting the deubiquitinated I-κB degradation within the proteasome. Interestingly, we found that USP14 was associated with RelA, a binding partner of I-κB, suggesting that RelA is the linker between USP14 and I-κB. Lipopolysaccharide (LPS) treatment induced serine phosphorylation of USP14 as well as further reducing I-κB levels in HA-USP14-overexpressed MLE12 cells as compared with empty vector transfected cells. Further, overexpression of HA-USP14 increased the LPS-, TNFα-, or Escherichia coli-induced IL-8 release in human lung epithelial cells. This study suggests that USP14 removes the ubiquitin chain of I-κB, therefore inducing I-κB degradation and increasing cytokine release in lung epithelial cells.
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