ArticleJournal of cell science2014
Cullin 5 destabilizes Cas to inhibit Src-dependent cell transformation.
Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.Circulation research · 2024Article
- Article
- Cul5 mediates taurine-stimulated mTOR mRNA expression and proliferation of mouse mammary epithelial cells.Amino acids · 2023Article
- Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis.Current biology : CB · 2022Article
- Regulatory Roles of the N-Terminal Intrinsically Disordered Region of Modular Src.International journal of molecular sciences · 2022Review
- Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration.The Journal of cell biology · 2021Article
- Article
- Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.Acta pharmaceutica Sinica. B · 2021Review
- Epigenetic silencing of the ubiquitin ligase subunit FBXL7 impairs c-SRC degradation and promotes epithelial-to-mesenchymal transition and metastasis.Nature cell biology · 2020Article
- The functions and properties of cullin-5, a potential therapeutic target for cancers.American journal of translational research · 2020Review
- Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1.The Journal of clinical investigation · 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
- PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells.Cancer research · 2018Article
- Agrin has a pathological role in the progression of oral cancer.British journal of cancer · 2018Article
- SOCS2 Binds to and Regulates EphA2 through Multiple Mechanisms.Scientific reports · 2017Article
- The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells.eLife · 2016Article
- The role of cullin 5-containing ubiquitin ligases.Cell division · 2016Review
- PAK4 promotes kinase-independent stabilization of RhoU to modulate cell adhesion.The Journal of cell biology · 2015Article
- Cell regulation by phosphotyrosine-targeted ubiquitin ligases.Molecular and cellular biology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphorylation-dependent protein ubiquitylation and degradation provides an irreversible mechanism to terminate protein kinase signaling. Here, we report that mammary epithelial cells require cullin-5-RING-E3-ubiquitin-ligase complexes (Cul5-CRLs) to prevent transformation by a Src-Cas signaling pathway. Removal of Cul5 stimulates growth-factor-independent growth and migration, membrane dynamics and colony dysmorphogenesis, which are all dependent on the endogenous tyrosine kinase Src. Src is activated in Cul5-deficient cells, but Src activation alone is not sufficient to cause transformation. We found that Cul5 and Src together stimulate degradation of the Src substrate p130Cas (Crk-associated substrate). Phosphorylation stimulates Cas binding to the Cul5-CRL adaptor protein SOCS6 and consequent proteasome-dependent degradation. Cas is necessary for the transformation of Cul5-deficient cells. Either knockdown of SOCS6 or use of a degradation-resistant Cas mutant stimulates membrane ruffling, but not other aspects of transformation. Our results show that endogenous Cul5 suppresses epithelial cell transformation by several pathways, including inhibition of Src-Cas-induced ruffling through SOCS6.
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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.