ArticleThe Journal of biological chemistry2012
Direct and indirect control of mitogen-activated protein kinase pathway-associated components, BRAP/IMP E3 ubiquitin ligase and CRAF/RAF1 kinase, by the deubiquitylating enzyme USP15.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Targeted recruitment of USP15 enhances CTLA4 surface levels and restricts its degradation.Life science alliance · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer.Nature communications · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Mutation ofCancers · 2022Article
- USP15 in Cancer and Other Diseases: From Diverse Functionsto Therapeutic Targets.Biomedicines · 2022Review
- Tip110/SART3-Mediated Regulation of NF-κB Activity by Targeting IκBα Stability Through USP15.Frontiers in oncology · 2022Article
- USP15: a review of its implication in immune and inflammatory processes and tumor progression.Genes and immunity · 2021Review
- Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code.Frontiers in pharmacology · 2021Review
- Spotlight on USP4: Structure, Function, and Regulation.Frontiers in cell and developmental biology · 2021Review
- BRCA1-associated protein inhibits glioma cell proliferation and migration and glioma stem cell self-renewal via the TGF-β/PI3K/AKT/mTOR signalling pathway.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- How to Inactivate Human Ubiquitin E3 Ligases by Mutation.Frontiers in cell and developmental biology · 2020Review
- Dysregulation in the Brain Protein Profile of Zebrafish Lacking the Parkinson's Disease-Related Protein DJ-1.Molecular neurobiology · 2019Article
- Discovery of peptide ligands targeting a specific ubiquitin-like domain-binding site in the deubiquitinase USP11.The Journal of biological chemistry · 2019Article
- The deubiquitylase USP15 regulates topoisomerase II alpha to maintain genome integrity.Oncogene · 2018Article
- Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation.The Journal of biological chemistry · 2018Article
- USP15 regulates type I interferon response and is required for pathogenesis of neuroinflammation.Nature immunology · 2017Article
- Molecular basis for specificity of the Met1-linked polyubiquitin signal.Biochemical Society transactions · 2016Review
- Use of focused ultrasonication in activity-based profiling of deubiquitinating enzymes in tissue.Analytical biochemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The opposing regulators of ubiquitylation status, E3 ligases and deubiquitylases, are often found to be associated in complexes. Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. We map the interaction to the N-terminal DUSP-UBL domain of USP15 and the coiled coil region of BRAP. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15. Importantly, USP15 but not USP4 depletion destabilizes BRAP by promoting its proteasomal degradation, and BRAP-protein levels can be rescued by reintroducing catalytically active but not inactive mutant USP15. Unexpectedly, USP15 depletion results in a decrease in amplitude of MAPK signaling in response to EGF and PDGF. We provide evidence for a model in which the dominant effect of prolonged USP15 depletion upon signal amplitude is due to a decrease in CRAF levels while allowing for the possibility that USP15 may also function to dampen MAPK signaling through direct stabilization of a negative regulator, the E3 ligase BRAP.
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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.