Maciej B. Olszewski, Panagiotis Chandris, Bum-Chan Park, Evan Eisenberg and Lois E. Greene Disruption of Clathrin-Mediated Trafficking Causes Centrosome Overduplication and Senescence Traffic 15
Knocking out GAK, a HSC70 cochaperone essential for chaperoning clathrin causes senescence and centrosome overduplication. Disruption of clathrin-mediated endocytosis leads to alterations in mitogenic signaling profile which causes growth arrest and centrosome overduplication. Concurrent disruption of intracellular clathrin-dependent trafficking results in lysosomal membrane destabilization causing iron leakage that leads to DNA damage. Prolonged exposure to DNA damage in the presence of mitogenic stimulation leads to the development of senescence accompanied by centrosome overduplication.
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