ArticleCell cycle (Georgetown, Tex.)2014
Novel Lys63-linked ubiquitination of IKKβ induces STAT3 signaling.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- MARCH2-mediated Lys63-linked polyubiquitination promotes metastasis by modulating the catalytic activity of TGF-β type I receptor.Cell death & disease · 2025Article
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation.Oncotarget · 2022Article
- TRIMs: selective recruitment at different steps of the NF-κB pathway-determinant of activation or resolution of inflammation.Cellular and molecular life sciences : CMLS · 2021Review
- Heterozygous IKKβ activation loop mutation results in a complex immunodeficiency syndrome.The Journal of allergy and clinical immunology · 2021Article
- Substrate-specific recognition of IKKs mediated by USP16 facilitates autoimmune inflammation.Science advances · 2021Article
- Oncogenic fusion protein FGFR2-PPHLN1: Requirements for biological activation, and efficacy of inhibitors.Translational oncology · 2020Article
- Oncogenic fusion protein BCR-FGFR1 requires the breakpoint cluster region-mediated oligomerization and chaperonin Hsp90 for activation.Haematologica · 2020Article
- Sinomenine derivative YL064: a novel STAT3 inhibitor with promising anti-myeloma activity.Cell death & disease · 2018Article
- Oncogenic mutations in IKKβ function through global changes induced by K63-linked ubiquitination and result in autocrine stimulation.PloS one · 2018Article
- The Emerging Role of Non-traditional Ubiquitination in Oncogenic Pathways.The Journal of biological chemistry · 2017Review
- Ubc13: the Lys63 ubiquitin chain building machine.Oncotarget · 2016Review
- EcSTAT3ic about K63-Linked Ubiquitylation of IKKβ.Cell cycle (Georgetown, Tex.) · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NFκB signaling plays a significant role in human disease, including breast and ovarian carcinoma, insulin resistance, embryonic lethality and liver degeneration, rheumatoid arthritis, aging and Multiple Myeloma (MM). Inhibitor of κB (IκB) kinase β (IKKβ) regulates canonical Nuclear Factor κB (NFκB) signaling in response to inflammation and cellular stresses. NFκB activation requires Lys63-linked (K63-linked) ubiquitination of upstream proteins such as NEMO or TAK1, forming molecular complexes with membrane-bound receptors. We demonstrate that IKKβ itself undergoes K63-linked ubiquitination. Mutations in IKKβ at Lys171, identified in Multiple Myeloma and other cancers, lead to a dramatic increase in kinase activation and K63-linked ubiquitination. These mutations also result in persistent activation of STAT3 signaling. Liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS) analysis identified Lys147, Lys418, Lys555 and Lys703 as predominant ubiquitination sites in IKKβ. Specific inhibition of the UBC13-UEV1A complex responsible for K63-linked ubiquitination establishes Lys147 as the predominant site of K63-ubiquitin conjugation and responsible for STAT3 activation. Thus, IKKβ activation leads to ubiquitination within the kinase domain and assemblage of a K63-ubiquitin conjugated signaling platform. These results are discussed with respect to the importance of upregulated NFκB signaling known to occur frequently in MM and other cancers.
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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.