SP600125 inhibits cap-dependent translation independently of the c-Jun N-terminal kinase pathway.
We investigated the effects of SP600125 (formerly called c-Jun N-terminal kinase (JNK) inhibitor II) on translation using cultured mouse cells. SP600125 (50 µM) treatment rapidly repressed overall protein synthesis, accompanied by a reduction in the mRNAs for housekeeping genes such as glyceraldehyde-3-phosphate dehydrogenase in the polysomal fraction. SP600125 decreased polysomes with a concomitant increase in free ribosomal subunits in the cytoplasm, suggesting that global translation was inhibited at the initiation step. A reporter analysis using exogenous mRNAs showed that SP600125 inhibited cap-dependent but not internal ribosome entry site-dependent translation. SP600125 significantly attenuated phosphorylation of components in the mTOR pathway, which is responsible for cap-dependent translation. In contrast to SP600125, short hairpin RNAs for JNK1 and JNK2 failed to affect overall protein synthesis. Collectively, SP600125 inhibits cap-dependent translation, independent of the JNK pathway.
Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
Masatoshi
M
Ito
Hiroshi
H
Kitamura
Chisato
C
Kikuguchi
Koji
K
Hase
Hiroshi
H
Ohno
Osamu
O
Ohara
D016475:3T3 Cells; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D000873:Anthracenes; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases