Analysis of the protein expression changes during taxol-induced apoptosis under translation inhibition conditions.
Taxol is currently used in chemotherapeutic treatments of different types of cancers. In this article, we demonstrate that taxol induces apoptosis and translation down-regulation in human embryonic kidney (HEK293T) cells. Antibody arrays are a promising new tool for the analysis of protein levels changes in cells responding to different stimuli. Using this approach, we have identified changes in the expression of 38 proteins (20 down-regulated and 18 up-regulated), implicated in several cellular processes mainly in apoptosis, cell cycle and signal transduction pathways, and also cytoskeleton proteins. Among them, we have confirmed a considerable decrease in the expression of p14(ARF) and a significant increase in the levels of dystrophin and c-Myc. It is known that c-Myc mRNA has an internal ribosome entry segment (IRES) element in its 5'UTR that could regulate its expression under global protein synthesis inhibition conditions. We demonstrate that after taxol treatment, the c-Myc IRES activity is maintained meanwhile cap-dependent activity is inhibited. In addition, an increase in c-Myc mRNA was also observed after taxol treatment. We conclude that taxol-induced c-Myc expression is regulated at both transcriptional and translational levels, the last of them by a mechanism mediated by IRES.
Piñeiro
David
D
Servicio Bioquímica-Investigación, Hospital Universitario Ramón y Cajal (Irycis), Ctra. Colmenar km 9,100, 28034, Madrid, Spain.
González
Víctor M
VM
Salinas
Matilde
M
Elena Martín
M
M
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D003598:Cytoskeletal Proteins / Q000235:genetics; D016189:Dystrophin / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D016271:Proto-Oncogene Proteins c-myc; D025803:Tumor Suppressor Protein p14ARF; D017239:Paclitaxel