[Effect of inactivating the p33ING1 tumor suppressor on the function of cell cycle "checkpoints" and genome stability].
Novel candidate tumor suppressor p33ING1 is known to regulate activity of the p53 protein. The effect of p33ING1 inactivation on the functioning of the cell cycle "checkpoints" and the frequency of chromosomal aberrations was examined. Transduction of the p33-GSEas genetic suppressor element, known to reduce the p53 activity, into p53-positive rat and human cells resulted in: (1) partial abolishment of ethylmetansulphonate- or colcemid-induced arrest of the G1-to-S transition in the G0-synchronized cultures; (2) abolishment of the block in the S phase by the DNA synthesis inhibitor, N-phosphonacetil-L-aspartate (PALA); (3) an increase of the number of spontaneous chromosomal breaks and sister-chromatid exchanges; (4) increased frequency of colchicine-induced polyploidy. Similar effects were observed upon transduction of the p53-GSE22 genetic suppressor element, known to reduce p53 transcriptional activity. Presumably, the effect of p33ING1 inactivation on the cell cycle checkpoints and genetic stability is associated with a decrease in p53 activity.
Turovets
N A
NA
Institute of Carcinogenesis, Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
Agapova
L S
LS
Kopnin
P B
PB
Tulina
N M
NM
Chumakov
P M
PM
Kopnin
B P
BP
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D004261:DNA Replication / Q000187:drug effects; D004268:DNA-Binding Proteins; D003703:Demecolcine / Q000494:pharmacology; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D016147:Genes, Tumor Suppressor; D016678:Genome; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011123:Polyploidy; D011506:Proteins / Q000235:genetics*; D051381:Rats; D012854:Sister Chromatid Exchange; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D001224:Aspartic Acid; C013195:sparfosic acid; D005020:Ethyl Methanesulfonate; D010746:Phosphonoacetic Acid; D003703:Demecolcine