P14(ARF): The Absence that Makes the Difference

P14(ARF):缺席决定一切

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Abstract

P14(ARF) is a tumor suppressor encoded by the CDKN2a locus that is frequently inactivated in human tumors. P14(ARF) protein quenches oncogene stimuli by inhibiting cell cycle progression and inducing apoptosis. P14(ARF) functions can be played through interactions with several proteins. However, the majority of its activities are notoriously mediated by the p53 protein. Interestingly, recent studies suggest a new role of p14(ARF) in the maintenance of chromosome stability. Here, we deepened this new facet of p14(ARF) which we believe is relevant to its tumor suppressive role in the cell. To this aim, we generated a monoclonal HCT116 cell line expressing the p14(ARF) cDNA cloned in the piggyback vector and then induced aneuploidy by treating HCT116 cells with the CENP-E inhibitor GSK923295. P14(ARF) ectopic re-expression restored the near-diploid phenotype of HCT116 cells, confirming that p14(ARF) counteracts aneuploid cell generation/proliferation.

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