title: Translation regulation after taxol treatment in NIH3T3 cells involves the elongation factor (eEF)2.
abstract: Changes to the translational machinery that occur during apoptosis have been described in the last few years. The two principal ways in which translational factors are modified during apoptosis are: (i) changes in protein phosphorylation and (ii) specific proteolytic cleavages. Taxol, a member of a new class of anti-tubulin drugs, is currently used in chemotherapeutic treatments of different types of cancers. We have previously demonstrated that taxol induces calpain-mediated apoptosis in NIH3T3 cells [Piñeiro et al., Exp. Cell Res., 2007, 313:369-379]. In this study we found that translation was significantly inhibited during taxol-induced apoptosis in these cells. We have studied the phosphorylation status and expression levels of eIF2a, eIF4E, eIF4G and the regulatory protein 4E-BP1, all of which are implicated in translation regulation. We found that taxol treatment did not induce changes in eIF2alpha phosphorylation, but strongly decreased eIF4G, eIF4E and 4E-BP1 expression levels. MDL28170, a specific inhibitor of calpain, prevented reduction of eIF4G, but not of eIF4E or 4E-BP1 levels. Moreover, the calpain inhibitor did not block taxol-induced translation inhibition. All together these findings demonstrated that none of these factors are responsible for the taxol-induced protein synthesis inhibition. On the contrary, taxol treatment increased elongation factor eEF2 phosphorylation in a calpain-independent manner, supporting a role for eEF2 in taxol-induced translation inhibition.
authors.affiliation: Departamento de Bioquímica-Investigación, Hospital Ramón y Cajal, 28034 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Piñeiro
authors.forename: Víctor M
authors.initials: VM
authors.lastname: González
authors.forename: Macarena
authors.initials: M
authors.lastname: Hernández-Jiménez
authors.forename: Matilde
authors.initials: M
authors.lastname: Salinas
authors.forename: M Elena
authors.initials: ME
authors.lastname: Martín
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate / Q000172:deficiency; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002154:Calpain / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D039561:Eukaryotic Initiation Factor-4E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D039642:Eukaryotic Initiation Factors; D051379:Mice; D041681:NIH 3T3 Cells; D017239:Paclitaxel / Q000494:pharmacology*; D020652:Peptide Elongation Factor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism