title: The ribosomal protein S26 regulates p53 activity in response to DNA damage.
abstract: Ribosomal proteins have emerged as novel regulators of the Mdm2-p53 feedback loop, especially in the context of ribosomal stress. RPS26 is a recently identified Diamond-Blackfan Anemia-related ribosomal protein and its role in p53 activation has not been previously explored. In this study we found knockdown of RPS26 induced p53 stabilization and activation via a RPL11-dependent mechanism, resulting in p53-dependent cell growth inhibition. Moreover, RPS26 has the ability to interact with Mdm2 and inhibits Mdm2-mediated p53 ubiquitination that leads to p53 stabilization upon overexpression. Importantly, we discovered that RPS26 knockdown impaired p53's ability to transcriptionally activate its target genes in response to DNA damage, without affecting its stability. Accordingly, the cells lost the ability to induce G2/M cell cycle arrest. We further found that upon RPS26 knockdown, the DNA damage induced recruitment of p53 to the promoters of its target genes and p53 acetylation were both greatly reduced. In addition, RPS26 can interact with p53 independent of Mdm2 and coexist in a complex with p53 and p300. These data establish a role of RPS26 in DNA damage response by directly influencing p53 transcriptional activity, and suggest that RPS26 acts distinctively in different scenarios of p53 activation. Our finding also implicates p53 transcriptional activity control as an important mechanism of p53 regulation by ribosomal proteins.
authors.affiliation: 1] State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China [2] Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Cui
authors.affiliation: 1] State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China [2] Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China [2] College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Lou
authors.affiliation: 1] State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China [2] Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Biology and State (China) Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: S-M
authors.initials: SM
authors.lastname: Ngai
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: G
authors.initials: G
authors.lastname: Shao
authors.affiliation: 1] State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China [2] Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Tang
mesh_terms: D000107:Acetylation; D029503:Anemia, Diamond-Blackfan / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C489203:RPS26 protein, human; D012269:Ribosomal Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2