Molecular interactions between telomerase and the tumor suppressor proteinp53 in vitro

The telomere DNA polymerase (telomerase) and the tumor suppressor protein p 53 are frequently associated with human cancers, and activation of telomera se and inactivation of p53 involved in cancer cell immortalization. In this report, we demonstrate a direct interaction of telomerase with p53 in the nuclear lysates of human breast cancer cells, and with recombinant human p5 3, by affinity chromatography and immunoprecipitation. On activity criteria , the interaction is between the carboxyl-terminal region of p53 and a regi on close to the amino-terminus of human telomerase-associated protein 1 (hT EP1). Incubation of recombinant p53 with nuclear telomerase extracts result s in inhibition of telomerase activity, with the C-terminal region of p53 b eing essential for inhibition. This effect is not mediated by binding to te lomerase substrate DNA, but requires the region near the N-terminus of hTEP 1, in that a synthetic peptide derived from this region of hTEP1 similarly inhibits telomerase activity. Together, these in vitro interactions between telomerase and p53 suggest that the activity of telomerase may be regulate d by p53, downregulation of which in turn would favor up-regulation of telo merase activity in cancer cell development.