[Dominant-negative inactivation of p53: the effect of the proportion between trans-dominant inhibitor and its target].
Dominant-negative mutations of the p53 tumor suppressor gene and oligomerization of the mutant and wild-type p53 are considered responsible for functional inactivation of the p53 tetramer. Although dominant-negative inactivation of p53 is well reproducible in experimental systems, its contribution to processes occurring in tumor cells heterozygous at p53 is still unclear. To study the effect of dominant-negative inhibitor GSE22 on the p53 activity, cultures coexpressing GSE22 and tetracycline-suppressible p53 were derived from p53-negative cell lines. Transcriptional activity and expression of p53 proved to depend on the proportion between p53 and GSE22. The dominant-negative effect was observed only when GSE22 was in a multifold excess to p53. GSE22 was shown to be suitable for complete reversible inactivation of p53.
Morgunkova
A A
AA
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia. morgunkova@yandex.ru
Almazov
V P
VP
Strunina
S M
SM
Kopnin
B P
BP
Chumakov
P M
PM
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005799:Genes, Dominant / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012190:Retroviridae / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; D013752:Tetracycline