title: 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.
authors.affiliation: Division of Cancer Biology, Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0936, USA.
authors.forename: H
authors.initials: H
authors.lastname: He
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D045325:HCT116 Cells / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008667:Metalloproteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008667:Metalloproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C083686:RPS27 protein, human; C586073:RPS27L protein, human; D012269:Ribosomal Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2