title: Ribosomal proteins as unrevealed caretakers for cellular stress and genomic instability.
abstract: Ribosomal proteins (RPs) have gained much attention for their extraribosomal functions particularly with respect to p53 regulation. To date, about fourteen RPs have shown to bind to MDM2 and regulate p53. Upon binding to MDM2, the RPs suppress MDM2 E3 ubiquitin ligase activity resulting in the stabilization and activation of p53. Of the RPs that bind to MDM2, RPL5 and RPL11 are the most studied and RPL11 appears to have the most significant role in p53 regulation. Considering that more than 17% of RP species have been shown to interact with MDM2, one of the questions remains unresolved is why so many RPs bind MDM2 and modulate p53. Genes encoding RPs are widely dispersed on different chromosomes in both mice and humans. As components of ribosome, RP expression is tightly regulated to meet the appropriate stoichiometric ratio between RPs and rRNAs. Once genomic instability (e.g. aneuploidy) occurs, transcriptional and translational changes due to change of DNA copy number can result in an imbalance in the expression of RPs including those that bind to MDM2. Such an imbalance in RP expression could lead to failure to assemble functional ribosomes resulting in ribosomal stress. We propose that RPs have evolved ability to regulate MDM2 in response to genomic instability as an additional layer of p53 regulation. Full understanding of the biological roles of RPs could potentially establish RPs as a novel class of therapeutic targets in human diseases such as cancer.
authors.affiliation: Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Tae-Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Patrick
authors.initials: P
authors.lastname: Leslie
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2