title: Therapeutic interventions to disrupt the protein synthetic machinery in melanoma.
abstract: Control of the protein synthetic machinery is deregulated in many cancers, including melanoma, to increase the protein production. Tumor suppressors and oncogenes play key roles in protein synthesis from the transcription of rRNA and ribosome biogenesis to mRNA translation initiation and protein synthesis. Major signaling pathways are altered in melanoma to modulate the protein synthetic machinery, thereby promoting tumor development. However, despite the importance of this process in melanoma development, involvement of the protein synthetic machinery in this cancer type is an underdeveloped area of study. Here, we review the coupling of melanoma development to deregulation of the protein synthetic machinery. We examine existing knowledge regarding RNA polymerase I inhibition and mRNA translation focusing on their inhibition for therapeutic applications in melanoma. Furthermore, the contribution of amino acid biosynthesis and involvement of ribosomal proteins are also reviewed as future therapeutic strategies to target deregulated protein production in melanoma.
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.|The Melanoma and Skin Cancer Center, Hershey, PA, USA.|The Melanoma Therapeutics Program, Hershey, PA, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Kardos
authors.affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.|The Melanoma and Skin Cancer Center, Hershey, PA, USA.|The Melanoma Therapeutics Program, Hershey, PA, USA.|Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.|Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.|Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Robertson
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D001120:Arginine / Q000737:chemistry; D049109:Cell Proliferation; D004275:DNA, Ribosomal / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D009841:Oligonucleotides / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D004275:DNA, Ribosomal; D015852:Eukaryotic Initiation Factor-2; D009841:Oligonucleotides; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D001120:Arginine; D011392:Proline; D019869:Phosphatidylinositol 3-Kinases; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase
keywords: amino acids; mRNA translation; melanoma; protein synthesis; ribosomal proteins