Human p53, mutated at codon 273, causes distinct effects on nucleotide biosynthesis salvage pathway key enzymes in Rat-1 cells and in their derivatives expressing activated ras oncogene.
The introduction of human p53 with mutation at codon 273 into Rat-1 cells induces changes in the salvage pathway of nucleotide synthesis. In cells expressing the mutant p53 the activities of hypoxanthine phosphoribosyl transferase (HPRT) and thymidide kinase (TK) decrease 3.5- and 2-3-fold, respectively, while the activities of adenosine deaminase and uridine kinase, in contrast, increase correspondingly 2.5- and 1.5-fold. On the other hand, in cells transformed by ras oncogene, which causes dramatical reduction in HPRT activity as well as enhancement of TK function, the expression of exogeneous p53 leads to the opposite effects and causes the reversion of activities of both enzymes to the levels found in parental cells.
Khramtsova
S
S
Cancer Research Centre, Moscow, Russian Federation.
Stromskaya
T
T
Potapova
G
G
Chumakov
P
P
Kopnin
B
B
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003062:Codon / Q000235:genetics*; D011905:Genes, ras; D005822:Genetic Vectors; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007700:Kinetics; D008727:Methotrexate / Q000633:toxicity; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009711:Nucleotides / Q000096:biosynthesis*; D017354:Point Mutation; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D051381:Rats; D013937:Thymidine Kinase / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014541:Uridine Kinase / Q000378:metabolism
D003062:Codon; D009711:Nucleotides; D011687:Purines; D011743:Pyrimidines; D016159:Tumor Suppressor Protein p53; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase; D014541:Uridine Kinase; D000243:Adenosine Deaminase; D008727:Methotrexate