title: Activation of p53 protein by telomeric (TTAGGG)n repeats.
abstract: Genome instability is a primary factor leading to the activation of the p53 tumor suppressor protein. Telomeric repeat (TR) sequences are also responsible for genome integrity. By capping the termini of the chromosomes, TRs prevent them undergoing nucleolytic degradation, ligation or chromosome fusion. Interestingly, telomere shortening was suggested to activate p53, which in turn may cause primary cells to senesce. In order to elucidate the nature of a possible cross talk between the two, we introduced into cells TRs of defined length and investigated their effect on p53 activation and subsequent cellular response. We found that the introduction of a TR into cells leads to stabilization of the p53 protein. This stabilization was specific to TRs and was not observed in response to exposure of cells to plasmids containing non-TR sequences. p53 stabilization requires the presence of an intact p53 oligomerization domain. TR-activated p53 exhibited enhanced transcriptional activity. Eventually, TRs induced p53-dependent growth suppression, measured as a reduction in colony formation.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Milyavsky
authors.forename: A
authors.initials: A
authors.lastname: Mimran
authors.forename: S
authors.initials: S
authors.lastname: Senderovich
authors.forename: I
authors.initials: I
authors.lastname: Zurer
authors.forename: N
authors.initials: N
authors.lastname: Erez
authors.forename: I
authors.initials: I
authors.lastname: Shats
authors.forename: N
authors.initials: N
authors.lastname: Goldfinger
authors.forename: I
authors.initials: I
authors.lastname: Cohen
authors.forename: V
authors.initials: V
authors.lastname: Rotter
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D008156:Luciferases