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Gankyrin regulates Retinoblastoma and p53 proteins; key mediators of cellular senescence

Choi, Myong-Ho; Park, Tae Jun
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine
Gankyrin is a small oncoprotein (25 kDa) with seven ankyrin repeats sequence. Gankyrin is a subunit of the 26S proteasome that is consistently overexpressed in most of cancer. Gankyrin binds to retinoblastoma protein (Rb), and increases the phosphorylation and degradation of Rb, suggesting thatgankyrin promotes tumorigenicity and cancer cell proliferation. Furthermore, by binding to MDM2 which counteract the inhibitory function of p53, gankyrin acts as an accelerator for cell cycle progression. In this study, we investigated its relationship to cellular senescence. Highly expression of gankyrin was observed in U-87 cells and downregulation of gankyrin by shRNA induced cellular senescence. Flatted cell and increased SA-β-galactosidase expression were observed in gankyrin downregulated cells. Furthermore, gankyrin downregulation induced p53 accumulation. However, the detail mechanism of this interplay is underway.
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