Modulation of molecular mechanisms involved in protein synthesis machinery as a new tool for the control of cell proliferation.
In the past years, the attention of scientists has focused mainly on the study of the genetic information and alterations that regulate eukaryotic cell proliferation and that lead to neoplastic transformation. All therapeutic strategies against cancer are, to date, directed at DNA either with cytotoxic drugs or gene therapy. Little or no interest has been aroused by protein synthesis mechanisms. However, an increasing body of data is emerging about the involvement of translational processes and factors in control of cell proliferation, indicating that protein synthesis can be an additional target for anticancer strategies. In this paper we review the novel insights on the biochemical and molecular events leading to protein biosynthesis and we describe their involvement in cell proliferation and tumorigenesis. A possible mechanistic explanation is given by the interactions that occur between protein synthesis machinery and the proliferative signal transduction pathways and that are therefore suitable targets for indirect modulation of protein synthesis. We briefly describe the molecular tools used to block protein synthesis and the attempts made at increasing their efficacy. Finally, we propose a new multimodal strategy against cancer based on the simultaneous intervention on protein synthesis and signal transduction.
Caraglia
M
M
Dipartimento di Biochimica e Biofisica, Seconda Università di Napoli, Italy.
Budillon
A
A
Vitale
G
G
Lupoli
G
G
Tagliaferri
P
P
Abbruzzese
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D054736:Elongation Factor 2 Kinase; D006801:Humans; D020648:Peptide Elongation Factor 1 / Q000502:physiology; D010448:Peptide Initiation Factors / Q000502:physiology; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000187:drug effects; D000097574:Eukaryotic Translation Initiation Factor 5A
D000970:Antineoplastic Agents; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D054736:Elongation Factor 2 Kinase; D020648:Peptide Elongation Factor 1; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C517689:EEF2K protein, human