Growth inhibitory effects of large subunit ribosomal proteins in melanoma

Summary Ribosome biogenesis can modulate protein synthesis, a process heavily relied upon for cancer cell proliferation. In this study, involvement of large subunit ribosomal proteins ( RPL s) in melanoma has been dissected and RPL s categorized based on modulation of cell proliferation and therapeutic targeting potential. Based on these results, two categories of RPL s 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. RPL 13 represents the second category, where si RNA ‐mediated targeting inhibited tumor development through decreased cellular proliferation. Mechanistically, decreased RPL 13 levels increased p53 stability mediated by RPL 5 and RPL 11 binding to and preventing MDM 2 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 MDM 2‐p53 pathway.