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• W2022013480 abstract "Reactivation of telomerase is a feature in many cancer cells. Telomerase activation inhibits telomere shortening, thereby preventing cell cycle arrest and apoptosis activated by shortened telomeres or chromosomal rearrangements. The tumor-suppressor gene product, p53, was previously shown to transcriptionally suppress the activation of the catalytic subunit of telomerase (hTERT). Here we have evaluated the role of p73 in hTERT regulation. We found that ectoptic expression of p73β, in contrast to p73α or p53, in p53 null H1299 cells does not lead to suppression of <i>hTERT</i> transcription. However co-expression of p73α or p73β together with p53 abolished p53-mediated <i>hTERT</i> suppression. This phenomenon was found to be dependent on the DNA binding ability of p73. We also show that p53-mediated suppression of <i>hTERT</i> transcription requires a minimum threshold level of p53, and p73 abrogates p53-mediated suppression by reducing p53 levels through the activation of HDM2. Moreover, p53-mediated <i>hTERT</i> suppression was not relieved by p73β in cells depleted of HDM2 through small interfering RNA-mediated gene silencing. In addition, knockdown of HDM2 in MCF7 cells, which express moderately high levels of p73 and p53, resulted in the reduction of endogenous <i>hTERT</i> levels. Finally, knockdown of p73 in MCF7 cells resulted in increased p53 protein levels and a concomitant decrease in <i>hTERT</i> levels. Together, our data indicate a plausible way by which p73, through HDM2, can oppose p53 tumor suppressor function, thereby possibly contributing to tumorigenesis." @default.
• W2022013480 created "2016-06-24" @default.
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• W2022013480 date "2005-04-01" @default.
• W2022013480 modified "2023-10-11" @default.
• W2022013480 title "Relief of p53-mediated Telomerase Suppression by p73" @default.
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• W2022013480 doi "https://doi.org/10.1074/jbc.m500044200" @default.
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