title: Growth inhibitory effects of large subunit ribosomal proteins in melanoma.
abstract: Ribosome biogenesis can modulate protein synthesis, a process heavily relied upon for cancer cell proliferation. In this study, involvement of large subunit ribosomal proteins (RPLs) in melanoma has been dissected and RPLs categorized based on modulation of cell proliferation and therapeutic targeting potential. Based on these results, two categories of RPLs were identified: the first causing negligible effects on cell viability, p53 expression, and protein translation, while the second category decreased cell viability and inhibited protein synthesis mediated with or without p53 protein stabilization. RPL13 represents the second category, where siRNA-mediated targeting inhibited tumor development through decreased cellular proliferation. Mechanistically, decreased RPL13 levels increased p53 stability mediated by RPL5 and RPL11 binding to and preventing MDM2 from targeting p53 for degradation. The consequence was p53-dependent cell cycle arrest and decreased protein translation. Thus, targeting certain category 2 RPL proteins can inhibit melanoma tumor development mediated through the MDM2-p53 pathway.
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA; The Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, PA, USA; The Melanoma Therapeutics Program, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Kardos
authors.forename: Mu-Shui
authors.initials: MS
authors.lastname: Dai
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Robertson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C085488:RPL13 protein, human; D012269:Ribosomal Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11; C549166:ribosomal protein L5, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: RP-MDM2-p53; cell cycle; melanoma; p53; protein synthesis; ribosomal proteins