ArticleThe Journal of biological chemistry2009
Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK ativation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.Frontiers in physiology · 2020Pooled it
- The deubiquitination enzyme USP14 promotes the tumourigenesis of gastric cancer by enhancing c-MYC nuclear translocation through deubiquitination of KPNA2.Cell death & disease · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- USP34 regulates endothelial PAR1 mRNA transcript expression and cellular signaling.Molecular biology of the cell · 2025Article
- USP39 at the crossroads of cancer immunity: regulating immune evasion and immunotherapy response through RNA splicing and ubiquitin signaling.Frontiers in immunology · 2025Review
- GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC.Mediators of inflammation · 2025Article
- Identification and verification of diagnostic biomarkers for deep infiltrating endometriosis based on machine learning algorithms.Journal of biological engineering · 2024Article
- Comprehensive characterization of high-risk coding and non-coding single nucleotide polymorphisms of human CXCR4 gene.PloS one · 2024Article
- USP14 Regulates ATF2/PIK3CD Axis to Promote Microvascular Endothelial Cell Proliferation, Migration, and Angiogenesis in Diabetic Retinopathy.Biochemical genetics · 2023Article
- Targeting ubiquitin specific proteases (USPs) in cancer immunotherapy: from basic research to preclinical application.Journal of experimental & clinical cancer research : CR · 2023Review
- Up-regulation of microglial chemokine CXCL12 in anterior cingulate cortex mediates neuropathic pain in diabetic mice.Acta pharmacologica Sinica · 2023Article
- An Overview of the Mechanisms Involved in Neuralgia.Journal of inflammation research · 2023Review
- SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1.International journal of biological sciences · 2023Article
- USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer.Nature communications · 2022Article
- Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response.The Journal of biological chemistry · 2021Review
- Ubiquitin-specific peptidase 53 inhibits the occurrence and development of clear cell renal cell carcinoma through NF-κB pathway inactivation.Cancer medicine · 2021Article
- Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors.International journal of molecular sciences · 2021Review
- Development of a Novel SNAP-Epitope Tag/Near-Infrared Imaging Assay to Quantify G Protein-Coupled Receptor Degradation in Human Cells.SLAS discovery : advancing life sciences R & D · 2021Article
- Post-Translational Modifications of G Protein-Coupled Receptors Control Cellular Signaling Dynamics in Space and Time.Pharmacological reviews · 2021Review
- Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code.Frontiers in pharmacology · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The chemokine receptor CXCR4 plays important roles in the immune and nervous systems. Abnormal expression of CXCR4 contributes to cancer and inflammatory and neurodegenerative disorders. Although ligand-dependent CXCR4 ubiquitination is known to accelerate CXCR4 degradation, little is known about counter mechanisms for receptor deubiquitination. CXCL12, a CXCR4 agonist, induces a time-dependent association of USP14 with CXCR4, or its C terminus, that is not mimicked by USP2A, USP4, or USP7, other members of the deubiquitination catalytic family. Co-localization of CXCR4 and USP14 also is time-dependent following CXCL12 stimulation. The physical interaction of CXCR4 and USP14 is paralleled by USP14-catalyzed deubiquitination of the receptor; knockdown of endogenous USP14 by RNA interference (RNAi) blocks CXCR4 deubiquitination, whereas overexpression of USP14 promotes CXCR4 deubiquitination. We also observed that ubiquitination of CXCR4 facilitated receptor degradation, whereas overexpression of USP14 or RNAi-induced knockdown of USP14 blocked CXCL12-mediated CXCR4 degradation. Most interestingly, CXCR4-mediated chemotactic cell migration was blocked by either overexpression or RNAi-mediated knockdown of USP14, implying that a CXCR4-ubiquitin cycle on the receptor, rather than a particular ubiquitinated state of the receptor, is critical for the ligand gradient sensing and directed motility required for chemokine-mediated chemotaxis. Our observation that a mutant of CXCR4, HA-3K/R CXCR4, which cannot be ubiquitinated and does not mediate a chemotactic response to CXCL12, indicates the importance of this covalent modification not only in marking receptors for degradation but also for permitting CXCR4-mediated signaling. Finally, the indistinguishable activation of ERK by wild typeor 3K/R-CXCR4 suggests that chemotaxis in response to CXCL12 may be independent of the ERK cascade.
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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.