Genre
- Journal Article
Mammalian ribonucleotide reductase is a highly regulated activity essential for DNA synthesis and repair. The activity and message levels of the enzyme are elevated in cells treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, and this appears to be mediated through specific cis elements in the 3'-untranslated region of the R1 and R2 mRNAs that interact with R1 and R2 binding proteins called R1BP and R2BP, respectively. Hydroxyurea-resistant cells with increased R1 and R2 message levels were observed to have increased R1 and R2 message half-lives. This was accompanied by alterations in R1 and R2 3'-untranslated region cis-trans interactions, as judged by band shift and UV crosslinking assays, in which R1BP and R2BP binding was markedly reduced. This first description of mutant mammalian cells altered in message stability regulatory determinants indicates another mechanism for acquiring resistance to an antitumor agent. Furthermore, the present study strongly supports the concept that R1BP and R2BP are important general regulators of ribonucleotide reductase message stability and act as message destabilizing factors.
UNIV MANITOBA,MANITOBA INST CELL BIOL,WINNIPEG,MB R3E 0V9,CANADA. UNIV MANITOBA,DEPT BIOCHEM & MOLEC BIOL,WINNIPEG,MB R3E 0V9,CANADA.
PHILADELPHIA; PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106
AMER ASSOC CANCER RESEARCH
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Source type: Electronic(1)
Language
- English
Subjects
- ONCOLOGY
- FERRITIN
- PROTEIN
- INVOLVEMENT
- GENE
- EXPRESSION
- LINE