[Construction of chimeric tumor suppressor p53 resistant to the dominant-negative interaction with p53 mutants].
A chimeric p53 cDNA was constructed so that the fragment coding for 39 residues of the chicken p53 tetramerization domain replaced the corresponding region of human p53. The chimeric cDNA substantially inhibited the colony-forming ability of transfected human and mouse cells, suggesting a suppressory potential for its product. The chimeric p53 activated promoters containing p53-responsive elements. In contrast to wild-type human p53, the chimeric p53 remained capable of transcription activation in the presence of dominant-negative mutant p53-His175. This makes the chimeric p53 a convenient model for elaborating gene therapy protocols for tumors with dominant-negative p53 forms. The chimeric p53 may be used to study the role of transdominance of p53 mutants in carcinogenesis and the interactions of p53 with related transcription factors (p73, p63).
Almazov
V P
VP
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia. almazov@imb.ac.ru
Morgunkova
A A
AA
Kalinin
V N
VN
Kopnin
B P
BP
Prasolov
V S
VS
Chumakov
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D005799:Genes, Dominant; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D015202:Protein Engineering / Q000379:methods; D011994:Recombinant Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53