P14ARF: The Absence that Makes the Difference. 2020

Danilo Cilluffo, and Viviana Barra, and Aldo Di Leonardo
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128 Palermo, Italy.

P14ARF is a tumor suppressor encoded by the CDKN2a locus that is frequently inactivated in human tumors. P14ARF protein quenches oncogene stimuli by inhibiting cell cycle progression and inducing apoptosis. P14ARF 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 p14ARF in the maintenance of chromosome stability. Here, we deepened this new facet of p14ARF 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 p14ARF cDNA cloned in the piggyback vector and then induced aneuploidy by treating HCT116 cells with the CENP-E inhibitor GSK923295. P14ARF ectopic re-expression restored the near-diploid phenotype of HCT116 cells, confirming that p14ARF counteracts aneuploid cell generation/proliferation.

UI MeSH Term Description Entries
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000782 Aneuploidy The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1). Aneuploid,Aneuploid Cell,Aneuploid Cells,Aneuploidies,Aneuploids,Cell, Aneuploid,Cells, Aneuploid
D012521 Sarcosine An amino acid intermediate in the metabolism of choline. Methylglycine,Magnesium Sarcosylate,N-Methylglycine,Sarcosine Hydrochloride,Sarcosine Monosodium Salt,Sodium Sarcosinate,N Methylglycine,Sarcosinate, Sodium,Sarcosylate, Magnesium
D045325 HCT116 Cells Human COLORECTAL CARCINOMA cell line. HCT 116 Cells,HCT-116 Cells,Cell, HCT 116,Cell, HCT-116,Cell, HCT116,Cells, HCT 116,Cells, HCT-116,Cells, HCT116,HCT 116 Cell,HCT-116 Cell,HCT116 Cell
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D019086 Bridged Bicyclo Compounds, Heterocyclic Heterocyclic compounds that contain two rings that share two non-adjacent atoms in common. Bicyclo Compounds, Heterocyclic,Heterocyclic Cpds, Bicyclic,Bicyclic Heterocyclic Compounds,Heterocyclic Bicyclo Compounds,Bicyclic Heterocyclic Cpds,Heterocyclic Compounds, Bicyclic
D025803 Tumor Suppressor Protein p14ARF A gene product of the p16 tumor suppressor gene (GENES, P16). It antagonizes the function of MDM2 PROTEIN (which regulates P53 TUMOR SUPPRESSOR PROTEIN by targeting it for degradation). p14ARF is produced from the beta mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced alpha transcript, is CYCLIN-DEPENDENT KINASE INHIBITOR P16. Both p16 gene products have tumor suppressor functions. p14ARF Protein,Cdkn2a(p14ARF),p(ARF) Protein,p14(ARF),p14ARF

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