ArticleTraffic (Copenhagen, Denmark)2014
Disruption of clathrin-mediated trafficking causes centrosome overduplication and senescence.
Article in Traffic (Copenhagen, Denmark), 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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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
14 citing papers in PubMed, 18 citations in OpenAlex.
- The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors.Life science alliance · 2024Article
- Therapy-induced senescence in breast cancer: an overview.Exploration of targeted anti-tumor therapy · 2024Review
- MYL3 protects chondrocytes from senescence by inhibiting clathrin-mediated endocytosis and activating of Notch signaling.Nature communications · 2023Article
- The recurrent pathogenic Pro890Leu substitution in CLTC causes a generalized defect in synaptic transmission inFrontiers in molecular neuroscience · 2023Article
- Altered endocytosis in cellular senescence.Ageing research reviews · 2021Review
- Association ofFrontiers in genetics · 2021Article
- Structural Basis for the Inhibition of Cyclin G-Associated Kinase by Gefitinib.ChemistryOpen · 2018Article
- Spindle Assembly Disruption and Cancer Cell Apoptosis with a CLTC-Binding Compound.Molecular cancer research : MCR · 2018Article
- Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.Scientific reports · 2018Article
- GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase.Cell cycle (Georgetown, Tex.) · 2017Article
- Impaired ATP6V0A2 expression contributes to Golgi dispersion and glycosylation changes in senescent cells.Scientific reports · 2015Article
- The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain.Journal of cell science · 2015Article
- Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease.Autophagy · 2015Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The Hsc70 cochaperone, G cyclin-associated kinase (GAK), has been shown to be essential for the chaperoning of clathrin by Hsc70 in the cell. In this study, we used conditional GAK knockout mouse embryonic fibroblasts (MEFs) to determine the effect of completely inhibiting clathrin-dependent trafficking on the cell cycle. After GAK was knocked out, the cells developed the unusual phenotype of having multiple centrosomes, but at the same time failed to divide and ultimately became senescent. To explain this phenotype, we examined the signaling profile and found that mitogenic stimulation of the GAK KO cells and the control cells were similar except for increased phosphorylation of Akt. In addition, the disruption of intracellular trafficking caused by knocking out GAK destabilized the lysosomal membranes, resulting in DNA damage due to iron leakage. Knocking down clathrin heavy chain or inhibiting dynamin largely reproduced the GAK KO phenotype, but inhibiting only clathrin-mediated endocytosis by knocking down adaptor protein (AP2) caused growth arrest and centrosome overduplication, but no DNA damage or senescence. We conclude that disruption of clathrin-dependent trafficking induces senescence accompanied by centrosome overduplication because of a combination of DNA damage and changes in mitogenic signaling that uncouples centrosomal duplication from DNA replication.
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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.