ArticleCurrent biology : CB2009
Restriction of Src activity by Cullin-5.
Article in Current biology : CB, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Discovery of neddylation E2s inhibitors with therapeutic activity.Oncogenesis · 2023Review
- Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis.Current biology : CB · 2022Article
- Review
- Regulatory Roles of the N-Terminal Intrinsically Disordered Region of Modular Src.International journal of molecular sciences · 2022Review
- N-terminus-independent activation of c-Src via binding to a tetraspan(in) TM4SF5 in hepatocellular carcinoma is abolished by the TM4SF5 C-terminal peptide application.Theranostics · 2021Article
- Historical retrospective of theMolecular and clinical oncology · 2020Review
- A window-of-opportunity clinical trial of dasatinib in women with newly diagnosed endometrial cancer.Cancer chemotherapy and pharmacology · 2019Article
- Cullin 5 is a novel candidate tumor suppressor in renal cell carcinoma involved in the maintenance of genome stability.Oncogenesis · 2019Article
- Comparative Analysis of cul5 and rbx2 Expression in the Developing and Adult Murine Brain and Their Essentiality During Mouse Embryogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Article
- Article
- PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis.Nature communications · 2017Article
- SOCS2 Binds to and Regulates EphA2 through Multiple Mechanisms.Scientific reports · 2017Article
- Neddylation E2 UBE2F Promotes the Survival of Lung Cancer Cells by Activating CRL5 to Degrade NOXA via the K11 Linkage.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- miRNA expression profiling of Epstein-Barr virus-associated NKTL cell lines by Illumina deep sequencing.FEBS open bio · 2016Article
- Article
- The role of cullin 5-containing ubiquitin ligases.Cell division · 2016Review
- Impaired Reelin-Dab1 Signaling Contributes to Neuronal Migration Deficits of Tuberous Sclerosis Complex.Cell reports · 2015Article
- Cell regulation by phosphotyrosine-targeted ubiquitin ligases.Molecular and cellular biology · 2015Review
- MicroRNA-mediated transformation by the Kaposi's sarcoma-associated herpesvirus Kaposin locus.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Src is a nonreceptor tyrosine kinase that coordinates responses to diverse soluble and adhesive signaling molecules and regulates cell proliferation, survival, differentiation and migration. Normally, Src activity is tightly regulated, and Src-catalyzed phosphorylation is counterbalanced by phosphotyrosine phosphatases. However, deregulated mutant Src causes malignant transformation when highly expressed. Src transformation is dose dependent, but it has been unclear how much mutant Src, compared with endogenous Src, is required for transformation. Here, we show that transformation requires high-level overexpression of mutant src mRNA, in part because active Src protein is degraded by ubiquitin-mediated proteolysis. We show that active but not inactive Src protein is downregulated depending on the putative tumor suppressor and E3 ubiquitin ligase component, Cullin-5 (Cul5). Cul5 removal synergizes with physiological levels of mutant src mRNA to increase protein tyrosine phosphorylation, induce morphological transformation, and deregulate growth. Cul5 also represses Src-induced tumorigenesis and regulates Src signaling in normal cells. These results suggest that, when Src is activated by mutation or physiological mechanisms, its effects are limited by Cul5, which downregulates active Src and its phosphorylated substrates. These findings demonstrate the importance of a new mechanism that downregulates Src signaling in cells.
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What OpenQuestion holds
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.