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  • Original Article
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Ribosomal protein S27L is a direct p53 target that regulates apoptosis

Abstract

Ribosomal proteins were recently shown to regulate p53 activity by abrogating Mdm2-induced p53 degradation (L23, L11, L5) or by enhancing p53 translation (L26). Here, we report that a novel ribosomal protein, RPS27L (S27-like protein), is a direct p53 target. RPS27L, but not its family member RPS27, was identified as a p53 inducible gene in a genome-wide chip-profiling study. Further characterization revealed a p53-dependent induction of RPS27L in multiple cancer cell models. Indeed, a consensus p53-binding site was identified in the first intron of the RPS27L gene and a direct binding of p53 to this site was demonstrated both in vitro and in vivo. Characterization of a luciferase reporter driven by the RPS27L intron fragment revealed a p53-binding site-dependent transaction by wild-type p53, but not by several transactivating-deficient p53 mutants. This transactivation was enhanced by etoposide, a DNA damaging agent that activates p53 and was completely blocked by a dominant-negative p53 mutant. Functionally, overexpression of RPS27L within the physiological inducible levels promoted, whereas siRNA silencing of RPS27L inhibited, apoptosis induced by etoposide. This is the first report, to our knowledge, that p53 directly induces the expression of a ribosomal protein, RPS27L, which in turn promotes apoptosis.

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Acknowledgements

We thank Dr Ihor Lemischka at the Princeton University for the H1 plasmid for lenti-virus based siRNA silencing; Dr Colin Duckett at the University of Michigan for FG9 lenti-virus vector to make lenti-HA-RPS27L. We also thank Dr Bert Vogelstein at the Johns Hopkins University for HCT116-p53+/+ and HCT116-p53−/− cells. This work is supported by NCI grant (1R01-CA111554).

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Correspondence to Y Sun.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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He, H., Sun, Y. Ribosomal protein S27L is a direct p53 target that regulates apoptosis. Oncogene 26, 2707–2716 (2007). https://doi.org/10.1038/sj.onc.1210073

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