p53 polymorphic variants at codon 72 exert different effects on cell cycle progression.
Two common polymorphic forms of the p53 tumor suppressor protein are widely distributed throughout the human population. These encode either proline or arginine at position 72, and this difference results in a marked alteration in the primary structure of the protein. A number of previous studies have shown significant differences in the biochemical properties of the p53 protein, depending on the particular polymorphic form. There is little information, however, on their respective biologic activities. In this study, we have used an inducible switch system for expressing both polymorphic forms of p53 within Saos-2 cells. Cell cycle analysis postinduction of p53 function reveals striking differences in how the 2 forms of p53 bring about a cessation of cell growth. Thus, the Arg72 form of p53 is significantly more efficient than the Pro72 form at inducing apoptosis. In contrast, the Pro72 form appears to induce a higher level of G1 arrest than the Arg72 form. These results demonstrate significant differences in how the codon 72 polymorphism affects the biological activity of p53.
Pim
David
D
International Center for Genetic Engineering and Biotechnology, Trieste, Italy. pim@icgeb.org
Banks
Lawrence
L
D017209:Apoptosis; D001120:Arginine / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D003062:Codon / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D003062:Codon; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D001120:Arginine; D011392:Proline