Premium
Growth inhibitory effects of large subunit ribosomal proteins in melanoma
Author(s) -
Kardos Gregory R.,
Dai MuShui,
Robertson Gavin P.
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12259
Subject(s) - ribosome biogenesis , cell growth , protein subunit , translation (biology) , ribosomal protein , biology , protein biosynthesis , ribosome , microbiology and biotechnology , melanoma , cell cycle , viability assay , biogenesis , cell , cancer research , rna , biochemistry , messenger rna , gene
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.