ArticleThe Journal of biological chemistry2016
Kelch-like Protein 21 (KLHL21) Targets IκB Kinase-β to Regulate Nuclear Factor κ-Light Chain Enhancer of Activated B Cells (NF-κB) Signaling Negatively.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Deciphering the similarities and disparities of molecular mechanisms behind respiratory epithelium response to HCoV-229E and SARS-CoV-2 and drug repurposing, a systems biology approach.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- A novel microRNA-182/Interleukin-8 regulatory axis controls osteolytic bone metastasis of lung cancer.Cell death & disease · 2023Article
- Profiling of peripheral blood B-cell transcriptome in children who developed coeliac disease in a prospective study.Heliyon · 2023Article
- Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity.Cells · 2022Article
- Tumor-promoting mechanisms of macrophage-derived extracellular vesicles-enclosed microRNA-660 in breast cancer progression.Breast cancer research and treatment · 2022Article
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- SSTP1, a Host Defense Peptide, Exploits the Immunomodulatory IL6 Pathway to Induce Apoptosis in Cancer Cells.Frontiers in immunology · 2021Article
- Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells.Cell reports · 2020Article
- KLHL5 Is a Prognostic-Related Biomarker and Correlated With Immune Infiltrates in Gastric Cancer.Frontiers in molecular biosciences · 2020Article
- Vaccinia Virus BBK E3 Ligase Adaptor A55 Targets Importin-Dependent NF-κB Activation and Inhibits CD8Journal of virology · 2019Article
- KLHL5 knockdown increases cellular sensitivity to anticancer drugs.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of IKKβ is the key step in canonical activation of NF-κB signaling. Extensive work has provided insight into the mechanisms underlying IKKβ activation through the identification of context-specific regulators. However, the molecular processes responsible for its negative regulation are not completely understood. Here, we identified KLHL21, a member of the Kelch-like gene family, as a novel negative regulator of IKKβ. The expression of KLHL21 was rapidly down-regulated in macrophages upon treatment with proinflammatory stimuli. Overexpression of KLHL21 inhibited the activation of IKKβ and degradation of IκBα, whereas KLHL21 depletion via siRNA showed the opposite results. Coimmunoprecipitation assays revealed that KLHL21 specifically bound to the kinase domain of IKKβ via its Kelch domains and that this interaction was gradually attenuated upon TNFα treatment. Furthermore, KLHL21 did not disrupt the interaction between IKKβ and TAK1, TRAF2, or IκBα. Also, KLHL21 did not require its E3 ubiquitin ligase activity for IKKβ inhibition. Our findings suggest that KLHL21 may exert its inhibitory function by binding to the kinase domain and sequestering the region from potential IKKβ inducers. Taken together, our data clearly demonstrate that KLHL21 negatively regulates TNFα-activated NF-κB signaling via targeting IKKβ, providing new insight into the mechanisms underlying NF-κB regulation in cells.
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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.